Anorexia nervosa (AN) is a serious mental disorder, characterized by severely low weight and cognitive distortions about body shape and weight. AN is generally associated with a constellation of psychological symptoms, including depression, anxiety, obsessionality, and ritualistic behaviors. The presence of these associated symptoms, together with the great challenge of treating patients with AN, has led clinicians to try many psychopharmacologic agents in the treatment of these patients, usually to no avail. Investigators have studied a range of agents, but have found little, if any, utility in treating underweight patients with medication. In this article, the authors review the literature regarding medication treatment for patients with AN, propose a theoretical basis for the poor response of these patients to the agents that have been tried, and conclude with recommendations for treatment strategies and additional research that should be pursued to further our understanding of this difficult illness.