Hyperinsulinism in infancy (HI) is a heterogeneous disorder with respect to clinical presentation, genetics, histology and response to therapy. Advances in the understanding of the molecular basis of the disease have given the pediatric endocrinologists a better insight into the diagnosis and therapeutic choice. In 50-60% of cases, a genetic etiology is unraveled. Mutations in the genes encoding SUR1 (ABCC8) and KIR6.2 (KCNJ11) are the most frequent genetic causes of HI followed by mutations in the GLUD1 gene which encodes glutamate dehydrogenase (GDH) enzyme. The patients with GLUD1 mutations also have hyperammonemia (HA). Activating dominant mutations in glucokinase (GCK) gene which result in HI are rare. In GLUD1 and GCK mutations the disease is usually mild, has a late onset and is responsive to diazoxide. However, studies so far have failed to show a clear genotype phenotype relation in KATP channel mutations. In conclusion the genetic analysis of HI has provided valuable information to the clinicians about the beta cell.