Proteolysis is a key regulatory post-translational modification in diverse cellular processes including programed cell death, immune function, and development. Tracking proteolytic events has become a focus of researchers assessing the downstream consequences of protease activation. In this review we summarize unbiased methods for identifying protease substrates and tracking the extent of cleavage, a field termed 'degradomics'. These include one-dimensional and two-dimensional gel-based methods for identifying protease substrates, N-terminal peptide identification methods for simultaneously identifying substrates and cleavage sites, and approaches for the quantitation of cleavage events during endogenous proteolysis. Individual methods have identified more than 300 caspase-cleaved targets during apoptosis suggesting broad future applications for these technologies.