The newly described CATERPILLER family (also known as NOD-LRR or NACHT-LRR) is comprised of proteins with a nucleotide-binding domain and a leucine-rich region. This family has gained rapid prominence because of its demonstrated and anticipated roles in immunity, cell death and growth, and diseases. CATERPILLER proteins are structurally similar to a subgroup of plant-disease-resistance (R) proteins and to the apoptotic protease activating factor 1 (APAF1). They provide positive and negative signals for the control of immune and inflammatory responses, and might represent intracellular sensors of pathogen products. Most importantly, they are genetically linked to several human immunological disorders.