The characters of Peter and Brian are very similar to Larry and Steve from the shorts The Life of Larry and What a Cartoon: Larry & Steve, which feature a moronic man who adopts a talking dog and puts the dog through hell, and were both written and directed by Seth MacFarlane
Before Seth MacFarlane created the idea of a regular half-hour series, he conceived of the Griffin family appearing as characters in animated shorts to appear on MADtv. Many of the regular voice actors (including Alex Borstein, Phil LaMarr, Debra Wilson and Nicole Sullivan) are "MADtv: alumni. Alex Borstein was the first cast on this show and is the only "official" cast member as the voice of Lois Griffin.
"Quahog," the name of the Griffin's hometown, is also the name of an edible clam. The bar the characters frequently visit, "The Drunken Clam", is a reference to this.
Brian's voice is simply Seth MacFarlane speaking normally. In addition, many of Brian's personal beliefs, including his generally liberal political views and his atheism, are shared by MacFarlane.
The original idea for titles of episodes were supposed to be based on 1940s Mystery Radio shows. This is why the first few episodes have some sort of reference to death in them. Eventually the writers of the show had to start describing the episodes to one another (rather than simply using the titles), so that idea was dropped.
Believing the series to be cancelled after season 2, many of the writers took on other jobs for different shows. The show was renewed for a third season at the last minute; many new writers were used for the new series.
The first part of the opening credits, where Lois plays the piano and sings with Peter, is a spoof of Edith playing the piano and singing with Archie during the opening credits of All in the Family
Bonnie Swanson would seemingly be pregnant throughout the entire series. Peter even mentions in Season 4, Episode 3, "Bonnie, you've been pregnant for like six years, alright? Either have the baby or don't." She finally gave birth to a girl, Susie, in Season 7, Episode 7.
Meg goes to James Woods Reqional (with a "Q") High School, and Chris goes to Buddy Cianci Junior High in fictional Quahog, RI. James Woods is from Warwick, RI, and Vincent "Buddy" Cianci, Jr. is the former mayor of Providence, RI.
Brought back an unprecedented second time after its amazing DVD sales (record for best selling TV show on DVD), and its popularity on Cartoon Network's Adult Swim, which a few times had a higher Nielsen rating than broadcast television at that time slot.
The show has been canceled twice, once following the second season, which caused the show to not air a new episode for a year, and the second (and longest) being between the third and fourth seasons, from 2002 to 2005.
In the early seasons in the opening credits, the pictures on the wall of Chris, Meg and Stewie, in the background, have blurred faces. Later on however, their faces appear normally.
All of the high-end hotels seen on the show have Barrington in their name. Series creator Seth MacFarlane has stated they are named after the city of Barrington, Rhode Island, a very upscale community.
Seth MacFarlane has admitted that the family's constant abuse of Meg is a result of "a bunch of male writers not knowing how to write for a teenage girl".
The show's Emmy nomination for "Best Comedy Series" in 2009 marked the first time since The Flintstones that an animated series earned such a nomination.
Seth MacFarlane is a fan of the Star Trek franchise, explaining the frequent references to Star Trek in the show. In fact, MacFarlane even appeared in two episodes of Star Trek: Enterprise during Enterprise's final two years of production.
Seth MacFarlane graduated from the Rhode Island School of Design in Providence, R.I. The shell of the quahog clam (Mercenaria mercenaria) is the official Rhode Island State shell. A quahog is a pretty standard looking clam, except that it's big - about the size of a grown man's hand. Rhode Islanders like to eat them in clam chowder (not white chowder, but clear, made without milk). They also stuff the clams with a bread and clam stuffing and serve them for dinner. The area's Indians, the Narragansetts, called them "quahog" which means simply "clam". They used the purple part of the shells to make wampum, which was traded by Indian tribes throughout North America.
Joe Swanson originally had a son named Kevin, who was eventually written out of the series. His disappearance was later explained in "Stew-Roids" (#7.13) as that he had died in Iraq.
Numerous cutaway gags involve characters from the Jetsons and the Flintstones, who are arguably Hanna-Barbera's most famous characters. This is because Seth MacFarlane was a writer for Hanna-Barbera before creating Family Guy.
When Drew Barrymore was preparing the documentary Choose or Lose Presents: The Best Place to Start, she contacted Seth MacFarlane to appear on it and besides asked him to do a guest voice on the show. MacFarlane enjoyed so much her work as Mrs. Lockhart on season 4 that offered Barrymore the regular role of Jillian.
Brian is a struggling novelist. Throughout the series, everyone in the family has made jokes about his "unfinished novel". In the episode "Movin' Out (Brian's Song)", it is revealed that the title of Brian's novel is 'Faster Than The Speed of Love'. When he describes the story to Lois, it turns out to be a rip-off of the film Iron Eagle.
The re-runs on Cartoon Network's late night "Adult Swim" schedule are often shown uncut with curse words mostly uncensored and even with scenes cut from the Fox broadcast re-inserted.
Like real-life children, Chris and Meg share the facial/body features of their parents, Peter and Lois. Meg has the same hairstyle, nose, and mouth as Lois (although Lois is considered very attractive and Meg very ugly in the show's universe) and has brown hair and wears glasses like Peter. As for Chris, he has eyes like Lois and a nose, mouth and dimpled chin like Peter. Chris has one attribute he shares with neither parent: His blonde hair. However in the early pre-production stages of the series, Lois was supposed to have blonde hair but the creative team decided to make her a red head (See IMDb trivia elsewhere on page). Despite the change, they chose to leave Chris' hair blonde.
Peter's phrase of choice when climaxing during sex is "Shazam!" Cleveland's phrase of choice in the same situation is "...and boom goes the dynamite." (albeit spoken in an unexcited monotone voice as Cleveland usually speaks.)
In an interview with MaD Radio in September 2012, Rachael MacFarlane debunked an Internet rumor that she voiced the character of Meg Griffin in the pilot. She did not.