The number of pharmacological agents available for the management of diabetes mellitus has grown significantly in recent years. As the incidence of diabetes mellitus and obesity increases in our population, it is critical to understand the types of therapy available, considering their mechanism, potential benefits, and side effects, to choose a safe and effective therapy for each individual. Available pharmacologic agents target one or more mechanisms related to hyperglycemia, and some have additional cardiorenal-protective benefits, ideal for individuals with comorbid atherosclerotic cardiovascular disease or chronic kidney disease. Once a suitable pharmacological agent has been initiated, it is important to continually monitor tolerance and efficacy. It is also recommended to follow-up at a minimum every 3–6 months to prevent therapeutic inertia. As a health-care provider, it is important to understand the pharmacologic agents so that proper education can be conveyed to the individual with diabetes.