Overweight and obesity have become an urgent public health problem in the United States: approximately 61% of the adult population (97 million adults) are overweight or obese, where overweight is defined as a body mass index (BMI) >/= 25 and obesity is defined as a BMI >/= 30. Overweight and obesity increase the risk for developing many serious chronic diseases such as cardiovascular disease, type 2 diabetes, hypertension, dyslipidemia, and certain cancers. Increased morbidity due to obesity-related disorders begins within the normal weight range. Weight gain in adulthood per se, even in individuals who are normal weight, has deleterious health effects. Medications, particularly those commonly used in psychiatry and neurology, are a significant iatrogenic source of overweight and obesity. The weight gain potential of prescription medications should be considered in order to enhance patient compliance and reduce the risk of metabolic sequelae of weight gain. This article provides an overview of the weight-gain potential of several classes of drugs commonly used in psychiatric practice and considerations for clinicians in prescribing these medications.