A doctor informs Muriel that she's pregnant after she faints at a restaurant while celebrating her 42nd birthday with her family. While she and Henry are initially elated, they find themselves faced with a serious decision as they begin to realize all of the implications of having another child at this point of their lives.

Henry's free-spirited niece, April, shows up on his doorstep after moving from Delaware to start a song writing career, and he reluctantly allows her to stay in the guest bedroom of his apartment until she's able to get established. However, their relationship starts off on the wrong foot, and Henry hopes it isn't too late when he finally figures out why.

Muriel and Henry read a newspaper article about a nurse who had switched babies in the maternity ward of the hospital that Sara had been delivered at. They quickly set out to find if indeed Sara had been switched at birth. However, they aren't too pleased when they discover the only other baby girl in the maternity ward is now serving time in prison.

Jackie openly dreads a visit from an annoying, nerdy guy who had a crush on her when she was a kid. However, when Sara is the first to discover his physical appearance has changed completely and starts dating him, Jackie becomes extremely jealous and vindictive.

Muriel goes in for an amniocentesis, but she and Henry decline to learn the sex of the baby. This doesn't sit well with Henry's mischievous father Huey, who is in town to bury his deceased friend. In the meantime, Jackie makes an unexpected decision after taking part in a successful strike at her bank.

An older man dressed like a bum shows up at the Rushes' doorstep looking for the transvestite persona of Rafkin, their deceased former tenant, because they always got together for Thanksgiving dinner. Feeling bad for him for several obvious reasons, they invite him to join their own disastrous get together, and later find out that he too has a big secret that involves his appearance.

Hearing a story about a man who died intestate causes Henry to have a terrible nightmare, which compels him to finally make out his will. However, he soon regrets his decision to follow Monroe's advice to do it on videotape in the presence of his family.

Monroe enrolls in an assertiveness class on the advice of the Rush girls after being pushed around at a concert, but the class proves to work a little too well. Meanwhile, one of Henry's colleagues suggests Henry demand a raise from Mr. Wainwright.

Muriel unwisely commits herself to do a coveted helicopter photo shoot, which Henry demands she cancel due to her pregnancy. The back and forth fighting cause a big headache for the girls, who are forced to change their minds several times whether to cancel an elaborate surprise 25th anniversary party they had previously scheduled.

Jackie falls madly in love with a police officer who responds to a false burglary report at the apartment due to April sneaking in late one night after getting stuck on Alcatraz with her boyfriend. She immediately accepts his marriage proposal after just a few dates, refusing her parents' plea to consider the difficulties of being a police wife.

Henry is going up the wall with April keeping such late hours, spending time with her latest boyfriend. However, Henry and Muriel are in for a shock when they discover her boyfriend, Don is old enough to be her father. Henry puts his foot down and that's when Don asks April to move in with him, which she gladly accepts.

A fan of Henry's Cosmic Cow comic strip who has been sending him increasingly bizarre fan mail breaks into the apartment one night through the unlocked front door, kidnapping his puppet and vowing in a note to return before the end of the weekend. Interpreting the note as a threat on his life, Henry and Monroe set up a stakeout at the apartment with the help of a police officer, who abruptly leaves them to fend for themselves when he is called away.

April secretly arranges for her father Bill to meet face to face with his brother Henry, so they can attempt to reconcile after a petty childhood dispute caused them to stop speaking forty years ago. The effort may be for naught, however, when Bill eats a piece of cheesecake baked by Monroe, who did not realize it was an old Russian recipe for homemade poisoned rat bait.

Henry is contacted by a rival cartoonist who has perpetrated several practical jokes on him over the years, and Henry schemes with Monroe to pay him back during a dinner visit. However, when Henry is unable to stop the prank after the man claims he is dying, Henry feels obligated to assist him in an elaborate plan to cheat on his wife.

Upon realizing the birth of his third child is only six weeks away, Henry feels a sense of guilt for not spending enough time with his two daughters. He decides to invite them on a weekend ski trip, but the experience doesn't turn out quite the way he envisioned when the girls meet a couple of brothers and he discovers that Monroe packed the wrong suitcase in the car.

Muriel secretly asks her mother Iris stay with her until she recovers from childbirth, much to the chagrin of Henry, who has always found her to be overbearing. When Muriel unexpectedly takes a stand against her mother's nonstop criticism, it's up to Henry to straighten out the mess, and he learns a big secret about Muriel in the process.

Henry's generous offer to arrange a job interview for an attractive art student backfires when she begins showing affection for him, which puts him in the doghouse with an increasingly insecure Muriel and causes him to panic when Monroe tells him that she tried to jump out a window after her last break up. Henry and Muriel also host a Lamaze class in their apartment, which turns out to be a bad idea.

Just before heading off on a Las Vegas vacation, Henry reluctantly lends $100 to Sara, April, and Monroe so they can start a business selling home-baked cookies using Grandma Rush's recipe. However, a promising and profitable start quickly turns into a disaster that includes a trashed kitchen, hefty fines, a potential lawsuit, and a visit from the immigration service.

In order to reduce the cost of a trip to Europe, Jackie and Sara swap apartments with an English couple who wants to visit America. Henry's misgivings are confirmed when he accidentally opens a piece of their luggage that contains a high powered rifle, and concludes they are on a mission to assassinate a Russian ambassador.

Henry refuses to accept Sara's decision to drop out of college to become the weather announcer on a local television station, which causes her to announce that she's moving out in protest. Meanwhile, Monroe's clumsy method of wallpapering the baby's nursery has an unexpected outcome, and a wealthy family friend brings the Rushes a much appreciated gift.

April's father sends her his baby grand piano, and she takes up Monroe's offer to move it into the apartment with the help of a large friend for $20. This proves to be a big mistake when everyone gets trapped in the apartment just as Muriel begins feeling labor pains and Henry's just-married friend becomes desperate to be reunited with his bride.