The menin protein encoded by the MEN1 tumor suppressor gene is ubiquitously expressed and highly conserved evolutionarily. The combination of findings from current in vitro and in vivo studies has not yielded a comprehensive understanding of the mechanisms of menin's tumor suppressor activity or the specific role for menin in endocrine tumorigenesis, although its diverse interactions suggest possible pivotal roles in transcriptional regulation, DNA processing and repair and cytoskeletal integrity. This manuscript summarizes recent research findings including studies of global gene expression in MEN1-associated neuroendocrine tumors and pivotal changes in intracellular signaling pathways associated with neuroendocrine tumorigenesis. Finally, the clinical applications provided by the understanding of the effects of MEN1 gene mutations on neuroendocrine tumor development in patients with this familial cancer syndrome are discussed.