According to Deadline, the Frasier star will helm the network's comedy Vince Uncensored.
The show stars No Ordinary Family's Michael Chiklis as a man who decides to take a more honest approach to life.
Grammer directed a number of episodes of Frasier and has also stepped behind the camera for episodes of Hank, Out Of Practice and Everybody Hates Chris.
Last November, it was reported that Starz has picked up a pilot which stars and is produced by Grammer.
Vince Uncensored is being made by Conan O'Brien's production company Conaco.