Prolactin secreting adenomas (prolactinomas) are the most prevalent form of pituitary tumors in humans. Prolactinomas have been linked to estrogen exposure in humans and animals. However, the mechanism by which estrogen increases mitogenesis in lactotropes, as well as other estrogen responsive cells, is not well understood. Given the complex nature of steroid hormones and their wide array of actions, it seems plausible that there are multiple ways in which estrogen can exert its cell-transforming actions. Estrogen has a wide range of actions on cells depending on the cell type, receptor levels, and other factors present in the cell. A defect at any point could play a potential role in cell transformation. The source of such defects could be the result of any of a wide range of possibilities, including genetic predisposition, prolonged exposure to sufficient levels of the steroid hormone, or other insults to the cell which lead to altered responsiveness to estrogen in some way. This review discusses the recent advances that have been made in the area of understanding estrogen action in transformation of pituitary lactotropes.