[5] The restaurant has kept its original character, which includes high ceilings, dark wood paneling, and red booths.

The Screen Writers Guild was located across the street, and Stanley Rose's essential bookstore was right next door to the restaurant.

Many writers of the hard-boiled fiction that Rose preferred, who hung out in the back room of the bookstore, spent endless hours in the bar of Musso and Frank, including James M. Cain,[18] John Fante (who frequented the restaurant with famed journalist and historian Carey McWilliams),[19] Raymond Chandler, and Nathanael West.

[25] By the 1940s the restaurant was so firmly identified with the Los Angeles literary scene that aspiring writers, e.g. Charles Bukowski, would drink there in a conscious effort to imitate their role models.

[8] Important Los Angeles progressives and communists were identified with Musso and Frank (and Rose's bookstore as well).

[29] The restaurant kept a separate back room for its film industry clientele,[30] which included not only screenwriters, many of whom are listed above, but actors, producers and directors as well, including Tom Mix, Charlie Chaplin,[28] Harry Warner and his brother Jack,[17] Greta Garbo,[31] Humphrey Bogart, Frank Sinatra, Marlon Brando, Marilyn Monroe, William Frawley, Douglas Fairbanks, Mary Pickford,[6] Orson Welles,[32] Rudolph Valentino,[33] and Budd Schulberg.

Aspects of the building cited in the register include its glass brick windows, flagstone wall, recessed entrance, neon sign, and intact interior.

The restaurant is also mentioned in the novels The Day of the Locust (1939),[44] Paul Cain's Fast One (1933),[25] What Makes Sammy Run?