CD40 is a cell surface receptor that belongs to the tumor necrosis factor receptor family. It was first identified and functionally characterized on B lymphocytes; however, in recent years it has become clear that CD40 expression is much broader, as it is found on monocytes, dendritic cells, hematopoietic progenitors, endothelial cells and epithelial cells. Although initially identified for its activation properties, CD40 is also able to transduce negative signals in various cell types. It is presently accepted that CD40 plays a critical role in the regulation of immune responses. The past year has seen considerable progress in the identification of intracellular molecules mediating CD40 signaling. Furthermore, it has been established that ligation of CD40 ligand (CD40L) delivers signals to the CD40L bearing cells themselves. Finally, the critical role of CD40-CD40L interactions in the development of various disease states has been fully appreciated.