The truncated C-terminal portion of Bid (tBid) is an important intermedi-ate in ligand-induced apoptosis. tBid has been shown to be sensitive to pro-teasomal inhibitors and downregulated by activation of the epidermal growth factor (EGF) pathway. Here, we provide evidence that tBid is a substrate of the ubiquitin ligase Itch, which can specifically interact with and ubiquitinate tBid, but not intact Bid.