The majority of pituitary adenomas are trophically stable and change relatively little in size over many years. A comparatively small proportion behave more aggressively and come to clinical attention through inappropriate hormone secretion or adverse effects on surrounding structures. True malignant behaviour with metastatic spread is very atypical. Pituitary adenomas that come to surgery are predominantly monoclonal in origin and roughly half are aneuploid, indicating either ongoing genetic instability or transition through a period of genetic instability at some time during their development. Few are associated with the classical mechanisms of tumour formation but it is generally believed that the majority harbour quantitative if not qualitative differences in molecular composition compared to the normal pituitary. Despite their prevalence and the ready availability of biopsy material, at the present time, the precise molecular pathogenesis of the majority of pituitary adenomas remains unclear. This review summarizes current thinking.