In recent years, CD38 has emerged from a simple differentiation marker to a multifunctional cell surface protein. It can serve as an ectoenzyme that catalyzes the synthesis and hydrolysis of a Ca2+mobilizing agent, cyclic ADP-ribose. Since intracellular calcium plays a key role in cell signaling pathways leading to cell growth, apoptosis, and differentiation, the enzymatic functions of CD38 may contribute to an array of immunoregulatory functions. Ligation of CD38 with agonistic antibodies induces diverse effects in hematopoietic cells which range from growth stimulation to induction and prevention of apoptosis, induction of cytokines, and activation of certain kinases. Based on these observations a ligand for CD38 was recently identified and characterized. The natural ligand is capable of transducing signals similar to the agonistic antibody, following its interaction with cell surface CD38. Recent reports have suggested an association of CD38 in diverse human pathologies such as HIV, chronic B lymphocytic leukemia, myeloma, lymphoma, diabetes, and retinoic acid syndrome. This book offers the first single source on CD38 antigen and related molecules for new and experienced investigators. It will allow them to pose new and right questions in an attempt to elucidate the biological relevance and significance of these molecules in cancer, immunology, pharmacology and biochemistry.