Type 2 diabetes (T2D) is a widely prevalent disease with substantial economic and social impact for which multiple conventional and novel pharmacotherapies are currently available; however, the landscape of T2D treatment is constantly changing as new therapies emerge and the understanding of currently available agents deepens. This review aims to provide an updated summary of the pharmacotherapeutic approach to T2D. Each class of agents is presented by mechanism of action, details of administration, side effect profile, cost, and use in certain populations including heart failure, non-alcoholic fatty liver disease, obesity, chronic kidney disease, and older individuals. We also review targets of novel therapeutic T2D agent development. Finally, we outline an up-to-date treatment approach that starts with identification of an individualized goal for glycemic control then selection, initiation, and further intensification of a personalized therapeutic plan for T2D. •Type 2 diabetes (T2D) is a widely prevalent disease with significant comorbidities.•A personalized treatment approach is recommended.•The mechanism of action, administration, indications, side-effects and cost of the available antidiabetic drugs should be considered.•GLP-1 RA and SGLT-2 inhibitors offer favorable side-effect profile and excellent cardiovascular and renal outcomes.•Targets of novel therapeutic T2D agents currently in development are discussed.