This lecture by William V. Tamborlane, MD describes the special challenges in treating youth with type 1 diabetes mellitus (T1DM), especially with respect to achieving target blood glucose and glycosylated hemoglobin levels and minimizing the risk of severe hypoglycemia. The impact of recent advances in therapy, including rapid and long acting insulin analogs, insulin pumps and continuous glucose monitoring, on the management and clinical outcomes of children and adolescents with T1DM are discussed in detail. The potential for combining these advances towards the development of an artificial pancreas will be presented