The pituitary gland regulates diverse physiological functions, including growth, metabolism, reproduction, stress response, and ageing. Early genetic models in the mouse taught us that the pituitary is highly sensitive to genetic alteration of specific cell cycle regulators such as the retinoblastoma protein (pRB) or the cell cycle inhibitor p27(Kip1). The molecular analysis of human pituitary neoplasias has now corroborated that cell cycle deregulation is significantly implicated in pituitary tumorigenesis. In particular, proteins involved in cyclin-dependent kinase regulation or the pRB pathway are altered in nearly all human pituitary tumors. Additional cell cycle regulators such as PTTG1/securin may have critical roles in promoting genomic instability in pituitary neoplasias. Recent experimental data suggest that these cell cycle regulators may have significant implications in the biology of putative progenitor cells and pituitary homeostasis. Understanding how cell cycle regulation controls pituitary biology may provide us with new therapeutic approaches against pituitary diseases.