Abstract: Substrates and inhibitors for the cysteine protease Ich-1 are disclosed. These compounds are designed based on an optimal minimal substrate for Ich-1 and include reversible inhibitors, irreversible inhibitors, selectively reversible inhibitors, chromogenic substrates, fluorogenic substrates and radiolabeled substrates/inhibitors. Pharmaceutical compositions comprising the compounds of the invention are also provided. Methods for inhibiting the proteolytic activity of Ich-1, methods for detecting the presence of Ich-1 and methods for isolating Ich-1 using the compounds of the invention are also disclosed.