Nods, a growing family of proteins containing a nucleotide-binding oligomerization domain (NOD), are involved in the regulation of programmed cell death (PCD) and immune responses. Members of the family include Apaf-1, Ced-4, Nod1, Nod2, and the cytosolic products of plant disease resistance genes. The NOD module is homologous to the ATP-binding cassette (ABC) found in a large number of proteins with diverse biological function. The centrally located NOD promotes activation of effector molecules through self-association and induced proximity of binding partners. The C-terminal domain of Nods serves as a sensor for intracellular ligands, whereas the N-terminal domain mediates binding to dowstream effector molecules and activation of diverse signaling pathways. Thus, Nods activate, through the NOD module, diverse signaling pathways involved in the elimination of cells via PCD and the host defense against pathogens.