Insulin, the first treatment for diabetes, was discovered >90 years ago. Since then, many new types of insulin have become available, including analogs that more closely mimic the characteristics of endogenous insulin. In addition, oral antidiabetes drugs and other types of injectable therapies have been approved for the treatment of patients with type 2 diabetes. As newer treatments are approved for type 2 diabetes, the choice and-paradoxically-the complexity of treatment increases. The potential benefits of all treatment options must be carefully balanced against potential adverse events to truly analyze the overall efficacy, safety, tolerability, and potential long-term effects. The manner in which outcomes are assessed and the methods employed to make such assessments have changed over time. This review will address these issues as they are related to therapies for type 2 diabetes, including insulin, oral antidiabetes drugs, and incretin-based agents.