Multiple endocrine neoplasia type 1 (MEN1), a human familial tumor syndrome, results from mutations in the Men1 gene. Although much progress has been made in demonstrating the definitive role for menin in suppressing tumorigenesis in endocrine organs, the molecular pathways responsible for menin action in normal tissues and tumors remain poorly defined. Here, we review the recent progress on the molecular functions of menin in controlling cell proliferation, apoptosis, and DNA repair. The majority of these functions are largely executed by menin-mediated influencing of histone modifications and chromatin structure. These findings lead to a new model of understanding menin's tumor-suppressing function, providing insights into understanding of how menin regulates cell proliferation and the development of endocrine tumors. The new knowledge could also be translated into new strategies to improve therapeutic interventions against MEN1 and other endocrine diseases including diabetes.