Aldose reductase (AR) is an aldo-keto reductase that has been widely investigated as an enzyme crucially involved in the pathogenesis of chronic complications associated with diabetes mellitus. Recently it was established that AR also acts as a key mediator of certain oxidative and inflammatory signaling pathways that are involved in the development of different human pathologies, such as cardiovascular disorders, sepsis, and cancer. These findings have renewed interest in the search for new AR inhibitors (ARIs) with improved profiles as potential therapeutic agents. In this review, recent advances in the field and promising future directions for developing ARIs are discussed.