Approximately 1 million persons are now infected with human immunodeficiency virus (HIV) in the United States. Evidence exists that psychiatric disorders are common in patients with HIV and that these patients may not receive optimal care because their psychiatric disorders are a barrier to medical care, communication with clinicians, and adherence to medical recommendations. We describe herein a complex case seen at The Johns Hopkins Hospital with several psychiatric conditions that are common in our HIV clinic population. We describe the collaborative treatment of the patient by a multidisciplinary team including both medical and mental health practitioners. We briefly describe a coherent diagnostic and treatment approach to patients in HIV clinics and the supporting rationale from the literature. We discuss the need for comprehensive evaluation, a multidisciplinary treatment team, and therapeutic optimism.