Presentation and management of psychiatric illness in HIV-infected patients can pose a challenge for clinicians. Psychiatric illness can exist premorbidly or result from the progression and treatment of HIV infection, influencing the course of the illness both through behavior and putative biological factors. Mood disorders, anxiety, psychosis, delirium, dementia, and substance abuse disorders all factor heavily into the care of HIV-infected patients. Management, however, continues to draw on small and skewed datasets, and remains largely an extrapolation from seronegative patient experience. The following is a discussion of treatment considerations derived from recent literature, as well as a consideration of judgments that clinicians may make in the absence of available data. The use of antidepressants, stimulants, mood stabilizers, and antipsychotics is discussed, as are precautions that must be taken with the HIV population when using these medications, not only because of side effect vulnerability, but because of significant drug-drug interactions.