Ed Palermo has been leading his own big band for more than 25 years, an accomplishment all by itself. Prior to that he had performed or recorded with Aretha Franklin, Tito Puente, Eddie Palmieri, Celia Cruz, Lena Horne, Tony Bennett, Mel Tormé, Lou Rawls, Melba Moore, Debbie Gibson, the Spinners, and many others. He has also written and arranged for The Tonight Show, Maurice Hines, and Eddy Fischer, and his arranging talents were singled out by master arranger Gil Evans: "I first heard Ed Palermo's music in a small club in the SoHo section of Manhattan. He was using the instrumentation of a traditional 'big band' yet his arrangements and songs were anything but that. When I thought the music was going a certain direction, it would suddenly turn a corner. Ed has the ability to keep that important balance between cohesiveness and unpredictability. Ed Palermo's music is alive and represents now."

Palermo has done arrangements of composers ranging from Jimi Hendrix and the Beatles to Shostakovich and Milhaud. However, he is probably best known for his arranging of the music of Frank Zappa for his big band, which has been performing the Zappa repertoire steadily for two decades. In 1997 he released the critically acclaimed The Ed Palermo Big Band Plays the Music of Frank Zappa on Astor Place, featuring the band with guest musicians Mike Stern and Mike Keneally.

In July 2002, the Ed Palermo Big Band played at the Zappanale Festival in Bad Doberan, Germany, and a year later a Swedish version of the band performed at the Umeå Internationella Kammarmusik Festival in Sweden with guests Napoleon Murphy Brock and Keneally. Take Your Clothes Off When You Dance, their second recording of Zappa material, was released in May 2006. Three years later, Palermo and company returned with another Zappa-themed big-band effort, Eddy Loves Frank. Oh No!! Not Jazz!! Followed in 2014. In 2017 he delivered The Great Un-American Songbook, Volumes I II, which featured jazz reworkings of songs by British rock acts including the Beatles, Cream, the Rolling Stones, Radiohead, and more. ~ Sean Westergaard, Rovi