The urgent need to treat type 2 diabetes mellitus (T2DM), which is currently reaching epidemic proportions, has been a major focus of healthcare systems and policy makers worldwide. Pharmacological treatment and lifestyle interventions together with the control of cardiovascular risk factors are the main strategies to prevent or delay the onset of T2DM. The present review discusses the state of the art knowledge of effective therapeutic approaches (metformin, thiazolidinediones, nateglinides, α-glucosidase inhibitors, incretin-based and angiotensin-based therapies, weight reducers, statins, fibric acid derivatives), including surgery, and identifies the major lifestyle changes for specific target groups.