Programmed cell death 1 (PD-1) is an inducible immune modulatory receptor. Upon interaction with its ligands B7 homolog 1 (PD-L1) and B7-DC (PD-L2), PD-1 plays important roles in negative regulation of T cell responses to antigen stimulation and maintaining peripheral tolerance. In addition to the inducible expression pattern on conventional T cells, PD-1 is also found on regulatory T cells, follicular T and B cells, and antigen-presenting cells including activated dendritic cells and monocytes. Therefore, PD-1 may have a much broader functionality than expected in negative regulation of multiple arms of immune responses. In addition to cancer therapy, the manipulation of PD-1 and its ligands may hold great promise for therapeutic applications also in autoimmune and infectious diseases.