The demonstration of protein sequence and functional homology of the Caenorhabditis elegans programmed cell death gene product, CED-3, with human caspase-1 in 1993 triggered an explosion of research activities toward the understanding of molecular mechanisms of apoptosis. During the past 15 years, a plethora of knowledge has been obtained on the mammalian caspases, the homologs of CED-3, with regard to their distinct physiological functions, their substrates, different activation mechanisms, the signal transduction pathways that lead to their activation as well as their involvement in the pathogenesis of diseases. Such knowledge is beginning to be translated into new therapies for the treatment of human diseases.