Multiple Endocrine Neoplasia Type 1 (MEN1), a rare tumor syndrome that is inherited in an autosomal dominant pattern, is continuing to raise great interest for endocrinology, gastroenterology, surgery, radiology, genetics and molecular biology specialists. There have been two major clinical practice guidance papers that were published in the past two decades, with the most recent publication 8 years ago. Since then, several new insights on the basic biology and clinical features of MEN1 have appeared in the literature and those data are discussed in this review. The genetic and molecular interactions of the MEN1 encoded protein menin with transcription factors and chromatin modifying proteins in cell signaling pathways mediated by TGF-β/BMP, few nuclear receptors, Wnt/β-catenin and Hedgehog (Hh), and preclinical studies in mouse models have facilitated the understanding of the pathogenesis of MEN1-associated tumors and potential pharmacological interventions. The advancements in genetic diagnosis have offered a chance to recognize MEN1 related conditions in germline MEN1 mutation negative patients. There is a rapidly accumulating knowledge about clinical presentation in children, adolescents and pregnancy that is translatable into the management of these very fragile patients. The discoveries about the genetic and molecular signatures of sporadic neuro-endocrine tumors support the development of clinical trials with novel targeted therapies, along with advancements in diagnostic tools and surgical approaches. Finally, quality of life studies in patients affected by MEN1 and related conditions represent an effort necessary to develop a pharmacoeconomic interpretation of the problem. Because advances are being made both broadly and in focused areas, this timely review presents and discusses those studies collectively.