<p>Given the severe and often enduring course of anorexia nervosa—where nearly half of patients may not reach full recovery—careful consideration of pharmacotherapy is essential, as pharmacokinetics can be significantly altered in the context of malnutrition, low body weight, and cachexia. Providers prescribing or preparing medications for patients who have anorexia nervosa as a comorbid condition need to consider what medications are unsafe for patients while treating these other disease states. The objective of this review article is to explore pharmacotherapeutic considerations for managing comorbid conditions in underweight patients with anorexia nervosa. This review will examine pharmacokinetic changes of underweight patients, assess each major organ system affected, and consider the implications of concomitant pharmacotherapy. Given the limited knowledge on the topic, the study applied broad criteria to include peer-reviewed research, expert commentary, and gray literature from 1969 to 2024. The search focused on pharmacotherapeutic considerations for underweight patients with anorexia nervosa, excluding studies solely addressing treatment. The search yielded 651 records, with 14 articles meeting the inclusion criteria after screening. Despite limited evidence, the review highlights literature on organ system complications in underweight patients with anorexia nervosa and offers considerations for medications on the basis of these affected systems. This article reviews treatment considerations, emphasizing the risks of medications such as bupropion and the need for further research to improve management strategies.</p>