Patients with type 2 diabetes mellitus (T2DM) are unlikely to maintain glycemic control with monotherapy, and will eventually require therapy with multiple antihyperglycemic agents (AHAs). Combination therapy regimens with multiple AHAs may be complex and negatively impact patient adherence. Fixed-dose combinations (FDCs) are used successfully for management of numerous chronic diseases. Areas covered: This article includes a brief overview of the add-on approach of current treatment guidelines for T2DM and reviews the evidence supporting the utility of oral FDCs in the treatment of T2DM, including recently developed oral FDCs (2010-2016). Benefits regarding safety and tolerability, adherence and cost are also discussed. Finally, the barriers limiting the use of FDCs and how these barriers may be overcome are addressed. Expert commentary: Therapeutic strategies including FDCs need to be implemented on a larger scale. FDCs have the potential to simplify treatment regimens, improve adherence and provide long-term glycemic control.