Weight loss and anorexia are common problems that are associated with increased morbidity and mortality in the growing frail elderly population. Orexigenic agents are often prescribed in an attempt to improve appetite and lean muscle mass. Much of the data regarding their benefit comes from studies involving younger patients with illnesses such as acquired immunodeficiency syndrome or cancer. This article reviews the use and potential adverse events associated with these medications in frail elderly patients. This article also discusses the effects of the different antidepressants and antipsychotics on weight gain and appetite.