Indoleamine 2,3-dioxygenase (IDO) is a heme enzyme that initiates the oxidative degradation of the least abundant, essential amino acid, l-tryptophan, along the kynurenine pathway. This protein is normally expressed in the dendritic cells, macrophages, microglia, eosinophils, fibroblasts, endothelial cells, and most tumor cells. IDO activity is associated with immunosuppression and immune attenuation. Several studies showed that IDO can contribute to immune escape when expressed directly in tumor cells or when expressed in immunosuppressive antigen presenting cells such as tolerogenic dendritic cells or tumor associated macrophages. IDO also is a promising therapeutic target for the treatment of cancer, chronic viral infections, and other diseases characterized by pathological immune suppression.