This review summarizes the morphologic findings in patients with acromegaly correlated with data on hormone secretion and regulation in vivo and in vitro. The importance of careful morphologic analysis that allows recognition of the varied diseases that have similar manifestations is emphasized. The gaps in our knowledge of pathogenesis are glaring, but continued dedication to the investigation of structure-function correlations combined with a greater understanding of the molecular basis of disease will, no doubt, lead to new discoveries and elucidate the factors underlying pituitary tumorigenesis.