Insulin is the most effective hormone for regulating blood glucose levels and thus maintaining glucose homeostasis. Physiologically, blood glucose is kept within narrow limits by a complex interplay of insulin secretion and action. However, genetic, intrauterine, drug or environmental factors can alter both beta-cell function and insulin sensitivity in peripheral organs in a way that physiological counter-regulatory mechanisms can no longer compensate for either reduced insulin secretion or action. As a result, glucose tolerance is altered, with a risk of progression to overt diabetes mellitus. The diagnosis of diabetes mellitus is made when blood glucose levels are elevated in the fasting state or after glucose loading. The term “type 2 diabetes mellitus” encompasses a group of heterogeneous clinical pictures. This heterogeneity is based both on the complexity of underlying pathophysiological mechanisms, but also on the variability of distinct phenotypes. Classification of type 2 diabetes mellitus into clinically relevant clusters is important to develop personalized therapy regimens and to reduce metabolic complications. Current therapeutic strategies for type 2 diabetes mellitus aim at both improving beta-cell function and increasing insulin sensitivity.