Patients living with human immunodeficiency virus represent a growing population, and an increased number of central nervous system presentations can be expected over the next decade. Emerging data suggests that both HIV-seropositive patients and cocaine-abusing patients may be at special risk of seizure phenomena. This case report discusses the risks of new-onset seizure activity when these two risk factors converge, which is a common occurrence in this population. Data from the fields of neuroanatomy and neurovirology are presented to explain the heightened risk of this patient population and provide the practitioner with an improved understanding of the central nervous system complexities in HIV.