Caspases are proteases crucial for the elimination of cancer cells by apoptotic cell death. Eugenia Delgado, a PhD student in the team of Dr Markus Rehm, has now published the first study in which the contribution of caspase-2 to apoptosis initiation and execution was analysed inside individual living cells by highly sensitive biophysical FRET reporter assays (Biochim Biophys Acta. 2013 Oct;1833(10):2279-92). So far, approaches towards measuring caspase-2 activity were restricted to analyses in cell homogenates and extracts, yielded inconsistent results, and were often limited in sensitivity, thereby contributing to controversies regarding the role of caspase-2 during apoptosis. Furthermore, caspases overlap in substrate specificities, and caspase-8 as well as effector caspases may cleave optimal caspase-2 recognition motifs. The study found that limited proteolysis of caspase-2 substrates during extrinsic apoptosis initiation was attributable to caspase-8 rather than caspase-2. The contribution of caspase-2 to proteolytic activities during apoptosis execution was insignificant. In contrast to several previous studies, the authors demonstrate that caspase-2 substrate is predominantly cleaved by caspase-8 and effector caspases during canonical apoptosis signalling.