Wendell Pierce is not a trombonist. He started taking lessons when he was cast as a trombonist, so his handling of the instrument would look credible on-screen. When Antoine Batiste plays, a professional trombone player off-screen provides the actual music. In season 4, a version of this behind-the-scenes story plays out in one of Antoine's story lines, when Antoine is hired to teach a non-trombonist actor (Lanny Fox, played by Wilson Bethel) to fake playing the trombone credibly during a movie shoot.

Real New Orleans musicians or bands who appeared on the show as themselves include: Kermit Ruffins, Coco Robicheaux;, Donald Harrison Jr., Dr. John, John Boutte, Art Neville, Irma Thomas, Clarence 'Frogman' Henry, Troy 'Trombone Shorty' Andrews, the Dirty Dozen Brass Band, Galactic, and the Hot 8 Brass Band.

Many real New Orleans and New Orleans-area restaurants, bars, and other venues have been featured on the show, including: Lil' Dizzy's Cafe, Vaughan's, Cafe Du Monde, Mosca's Restaurant, Tipitina's, Dooky Chase's Restaurant, The Rock'n'Bowl, and The Blue Nile. Janette's fictional New Orleans restaurant, Desautel's, was "played" by the real-life restaurant Patois. Storylines have also focused on the real-life New York restaurant Le Bernadin and a fictionalized version of Momofuku Ko and Ssäm Bar. Those New York-set scenes were actually filmed on a soundstage in New Orleans.

Elizabeth Ashley was a close friend of Tennessee Williams. She is also one of the preeminent stage interpreters of his female characters. Starting with her performance as Maggie in a 1974 Broadway revival of "Cat on a Hot Tin Roof," she has played nearly all of Williams's female leads.

The title of the first and the last episode are a compound, resulting in "Do You Know What It Means to Miss New Orleans", which is a famous song written by Eddie DeLange and Louis Alter, first heard in the movie New Orleans in 1947, where it was performed by Louis Armstrong and sung by Billie Holiday.