A variety of psychosocial stressors are involved in living with HIV, maintaining a regimen of highly active antiretroviral therapy, and negotiating necessary self-care behaviors. Because health care providers are in regular contact with HIV-infected individuals in care, these contacts allow for the opportunity to assess and intervene on important variables related to quality of life and HIV outcomes. This article reviews information about four important behavioral aspects of HIV care: treatment adherence, depression, high-risk sex, and substance abuse. Efforts by health care providers to address these factors may result in better treatment outcomes, enhanced quality of life among HIV patients, and decreased HIV transmission.