Alpha-ketoglutarate (AKG) is an intermediate in the Krebs cycle involved in various metabolic and cellular pathways. As an antioxidant, AKG interferes in nitrogen and ammonia balance, and affects epigenetic and immune regulation. These pleiotropic functions of AKG suggest it may also extend human healthspan. Recent studies in worms and mice support this concept. A few studies published in the 1980s and 1990s in humans suggested the potential benefits of AKG in muscle growth, wound healing, and in promoting faster recovery after surgery. So far there are no recently published studies demonstrating the role of AKG in treating aging and age-related diseases; hence, further clinical studies are required to better understand the role of AKG in humans. This review will discuss the regulatory role of AKG in aging, as well as its potential therapeutic use in humans to treat age-related diseases.