Abstract: The identification of caspases as major regulators of apoptotic cell death in animals initiated a quest for homologous peptidases in other kingdoms. With the discovery of metacaspases in plants, fungi, and protozoa, this search had apparently reached its goal. However, there is compelling evidence that metacaspases lack caspase activity and that they are not responsible for the caspaselike activities detected during plant and fungal cell death. In this paper, we attempt to broaden the discussion of these peptidases to biological functions beyond apoptosis and cell death. We further suggest that metacaspases and paracaspases, although sharing structural and mechanistic features with the metazoan caspases, form a distinct family of clan CD cysteine peptidases.