Treatment of diabetes mellitus requires, at a certain stage of its course, drug intervention. This article reviews the properties of available antidiabetic medications and highlights potential targets for developing newer and safer drugs. Antidiabetic agents are grouped in the article as parts I, II and III according to the history of development. Part I groups early developed drugs, during the 20th century, including insulin, sulfonylureas, the metiglinides, insulin sensitizers, biguanides and α-glucosidase inhibitors. Part II groups newer drugs developed during the early part of the 21st century, the past decade, including GLP-1 analogs, DPP-VI inhibitors, amylin analogs and SGLT2 inhibitors. Part III groups potential targets for future design of newer antidiabetic agents with less adverse effects than the currently available antidiabetic drugs.