Adolescents comprise a growing proportion of people diagnosed with HIV or AIDS. Navigating adolescence while infected with HIV presents specific challenges not only to the youth but to their families and caregivers. As children enter their teen years, they have medical, physiologic, and psychosocial issues that differ greatly from both younger children and young adults. These issues include the limited number of medications available, mental illness (especially depression), and psychosocial issues such as distorted body image, sexual awareness, and problems with family and peer relations. Many of these issues are heightened in this population and can be important factors that can influence adherence. Awareness of these issues is important for health care providers, for if they understand not just the illness itself, but the psychosocial issues of the patient they are treating, the clinician can optimize treatments and adherence, and help these young persons successfully transition into adulthood.