The past half decade has seen a huge growth of research into programmed cell death, its role in disease and the factors that promote and control it. The caspase family of proteases is now thought to occupy a key position in the control of programmed cell death, apparently acting both in apical and basal positions in an activation cascade. Apical caspases become activated by specific signalling mechanisms, and then proceed to activate other 'effector' caspases. Activated caspases promote a feed forward cycle that disables the cell repair machinery, activates protein kinases and nucleases that further promote cell death, and dismantle the cytoskeleton in the classic apoptotic pattern. However growing knowledge of the numbers of family members (14), the differences between rodent and human caspase members and their different roles in transducing multiple death signals, has emphasised the complexity of their interactions in cell death programmes. Nevertheless, with the development of peptide caspase inhibitors that block many models of cell death in vitro and in vivo, the exciting possibility that caspase inhibition could represent a new therapeutic area has received considerable attention. In this talk I will provide a brief introduction to caspase structure, substrate binding and inhibitor interactions; I will also give a brief overview of the interactions of caspases with some other cell death signalling mechanisms to place their role in context. I will then summarise some of our own evidence that caspases are involved in neurodegeneration and what effects specific caspase inhibitors have in these model systems. I will end by describing the practical issues that the caspases present as possible novel therapeutic targets in neurodegenerative disease.