Anterior pituitary tumors may secrete trophic hormones with resultant peripheral clinical disorders, or they may be clinically silent. Hypothalamic hormones control anterior pituitary hormone secretion and cell proliferation and also have been implicated in tumor promotion in animal models. Pituitary tumors are, however, monoclonal in origin. Several activating oncogene mutations as well as allelic loss of tumor suppressor genes have been described. Interestingly, apparently sporadic pituitary tumors appear to exhibit genetic defects similar to those for MEN 1-associated tumors. The multistep process of pituitary tumorigenesis is becoming increasingly apparent, and its understanding will provide novel prognostic and therapeutic options for these patients.