The Nomenclature Committee on Cell Death has recently warned the scientific community when using terms such as ‘caspase-dependent versus caspase-independent cell death’to classify apoptotic versus nonapoptotic cell death. 1 We strongly agree with this recommendation and we want to add a word of caution concerning the use of broad-spectrum caspase inhibitors in elucidating apoptotic pathways. The pioneer work in the 1960s by Dr. Robert Smith has established proteolysis by cysteinyl proteinases as a major physiological and pathological process. 2 To date, 14 mammalian caspases have been identified from the discovery in 1993 that the Caenorhabditis elegans ced-3 gene encoded a homolog of the human interleukin-1β-processing enzyme. 3 A striking feature of caspases is their specific ability to recognize particular short peptide sequences and to cleave after an aspartate residue, which is unique among mammalian proteases (except for the serine protease granzyme B). The introduction of an aldehyde group at the C-terminus of such sequences resulted in the generation of reversible inhibitors, whereas chloromethylketone, diazomethylketone, acyloxymethylketone, fluoromethylketone or phenoxymethylketone at this position created inhibitors that irreversibly inactivated caspases through a covalent thioether adduct with the cysteine of the active site. 2, 4–9 First generations of peptidic ‘pan-caspase’inhibitors and caspase activity probes were developed in the 1990s by Enzyme Systems Products. These