Human immunodeficiency virus (HIV) infection can cause neuropsychiatric disorders such as cognitive impairment, behavioural difficulties or psychiatric symptoms –for instance, mania and psychosis. HIV patients with psychiatric comorbidities need an appropriate treatment which tackles the HIV infection as much as the particular mental symptoms. Here we present the case of a patient suffering from delusions, which turned out to be caused by encephalitis secondary to a previously unknown HIV infection. A review of psychosis in HIV-infected patients is also presented. This review is focused on the epidemiology, etiopathogenesis and clinical presentation of HIV-induced psychosis, as well as the recommended pharmacological treatment (antiretroviral therapy and antipsychotic medication) and the expected treatment response. We also present wide information concerning pharmacological interactions between antiretroviral and antipsychotic medications that we hope will help the clinician to better manage this complex condition.