Pituitary adenomas may hypersecrete hormones (including prolactin, growth hormone and adrenocorticotropic hormone, and rarely follicle-stimulating hormone, luteinizing hormone or TSH) or may be nonfunctional. Despite their high prevalence in the general population, these tumors are invariably benign and exhibit features of differentiated pituitary cell function as well as premature proliferative arrest. Pathogenesis of dysregulated pituitary cell proliferation and unrestrained hormone hypersecretion may be mediated by hypothalamic, intrapituitary and/or peripheral factors. Altered expression of pituitary cell cycle genes, activation of pituitary selective oncoproteins or loss of pituitary suppressor factors may be associated with aberrant growth factor signaling. Considerable information on the etiology of these tumors has been derived from transgenic animal models, which may not accurately and universally reflect human tumor pathophysiology. Understanding subcellular mechanisms that underlie pituitary tumorigenesis will enable development of tumor aggression markers as well as novel targeted therapies.