Caspases can further be distinguished based on their inherent differences in caspase substrate preference that are defined by the shape and electrostatic potential of the active site cleft [2] . Using positional scanning of peptide libraries, consensus recognition sequences have been proposed for each caspase and have led to the development of peptide substrates as well as inhibitors that typically consist of 4 amino acids (i.e. DEVD for caspase-3), followed by a fluorescent tag such as Afc (7-amino-4-trifluoro methylcoumarin) for a substrate or a 'warhead' such as fmk (fluoromethylketone) that covalently binds the enzyme for an inhibitor. These reagents are useful to investigate caspases that constitute the majority of caspase-like activity in a sample, as it may be assumed for active caspase-3 in highly apoptotic extracts [3] . However, with Km/kcat ratio differences of less than 10 fold for many widely used peptide substrates [4] , these reagents are not particularly useful for investigating the activity of a caspase present at lower concentrations in cell culture and tissue samples. In particular in developmental or signalling processes that do not involve cell death, intracellular caspase activity is likely under tight control by endogenous caspase inhibitors or the proteasome [5, 6] and the resulting low levels of activity are difficult to detect with peptide substrates.