Captive Asian elephants have been maintained in captivity by humans for over 4000 years. Despite this association, there is little published literature on the treatment of elephant diseases or methods of drug administration to these animals. Elephants in captivity are generally healthy and require few therapeutic interventions over the course of their lifetime. However, when they become acutely ill, treatment becomes a serious issue. The successful and consistent administration of therapeutics to elephants is formidable in an animal that presents significant limitations in drug delivery options. The single most important factor in administering drugs to an elephant is the animals cooperation in accepting the medication. Working around elephants can be very dangerous and this is magnified when working around sick or injured animals where the elephant is subject to increased stress, pain, and unusual situations associated with treatment. The large body size of the Asian elephant produces a separate set of issues. In this paper, methods of drug administration and their associated limitations will be reviewed. Considerations of medicating such large animals can serve to highlight the problems and principles of treatment that are inherent in these species.