In some early trailers Richard Pryor did the voice of Eddie.

The Learjet featured in the movie, was owned by John Travolta at the time the movie was made. Tail number N254JT. JT = John Travolta.

Richard Pryor was offered the voice role of Eddie, but turned it down due to ill health.

The picture was nominated for Worst Picture at the Hastings Bad Cinema Society's 13th Stinkers Bad Movie Awards in 1990.

In a 2016 interview with The Current, an online publication of The Criterion Collection, Amy Heckerling mentions that she had "sort of been forced into doing a sequel to Look Who's Talking (1989) for legal reasons, and it was just like, the story is over. That was not a fun experience."

One film in a late 1980s Hollywood cycle of "baby pictures". The movies include Baby Boom (1987), For Keeps? (1988), Immediate Family (1989), Three Men and a Baby (1987) (which was based on the then recent French film Three Men and a Cradle (1985)), She's Having a Baby (1988), and Look Who's Talking (1989), with the latter followed early in the 1990s with Look Who's Talking Too (1990).

When James, Mikey and Julie go to the cinema, a poster of Total Recall (1990) is seen, which James impersonates the star of that movie Arnold Schwarzenegger. Total Recall (1990) was released in the United States on 1st June 1990. Look Who's Talking Too (1990) was released in the United States on 14th December 1990.

James refers to Stuart as "Travis Buckle" (referencing the movie Taxi Driver (1976)) during an argument with Mollie. Ironically James's former occupation was as a taxi driver.

Trailer narrated by Percy Rodrigues.

Although the film is rated PG-13 in the United States. The 'F' word is used twice. Mikey has nightmares about a demonic teddy bear and Mr. Toilet. There's a tense moment which Mikey and Julie are in the apartment when it catches fire and Molly has a cesarean which a piece of severed Molly's gut is removed and is rather bloody and quite graphic.

3 years after the release of this film, a 2nd sequel entitled Look Who's Talking Now (1993) which concluded the Look Who's Talking trilogy was released on November 5th 1993. The final in the trilogy depicts the Ubriacco family becoming the owners of two dogs Rocks and Daphne (Voiced by Danny DeVito and Diane Keaton).