Neonatal diabetes mellitus (NDM) is a rare and genetically heterogenous disorder characterized by persistent hyperglycemia presenting before the age of 6 months. This chapter will delve into the two subtypes of NDM, transient (TNDM) and permanent (PNDM), and explore the differences in their presentation, underlying genetics, and treatments. We will highlight some practical issues the pediatric endocrinologist often comes across during the initial workup and assessment of these infants, including differential diagnoses and laboratory investigation. Advances over the past two decades have dramatically expanded our understanding of NDM, transforming care through the application of precision genetic medicine. NDM provides a landmark example of how the application of precision genetic medicine enables low-cost, gene-informed, durable therapy with excellent safety and glycemic outcomes.