In patients with type 2 diabetes, a progressive decline in glycemic control exacerbates the microvascular (retinopathy, neuropathy, and nephropathy) and macrovascular (cardiovascular disease, stroke, and peripheral arterial disease) complications associated with this disease. In a consensus statement, the American Diabetes Association and the European Association for the Study of Diabetes stated that the main goal of antidiabetes therapy is to achieve glycemic control, defined as a glycated hemoglobin of < 7%, although goals should be individualized to each patient, especially in patients at highest risk of cardiovascular disease events. However, because type 2 diabetes is a progressive disease, the response to oral antidiabetes (OAD) agents declines over time and the majority of patients are unable to maintain glycemic control, thus necessitating additional therapy. This requirement for additional antidiabetes therapies as the disease progresses suggests that more aggressive and earlier use of synergistic therapies may help achieve and prolong glycemic control. This review examines the efficacy of OAD therapies to address the unmet need for prompt and maintained glycemic control to the recommended goal in patients with type 2 diabetes, the factors that can affect the glycemic response to the various classes of OAD agents, and ways in which the management of hyperglycemia can be improved in patients with type 2 diabetes.