Due to the improved management of Human Immunodeficiency Virus (HIV), children with Perinatally-acquired HIV (PHIV) infection have been surviving into adolescence and adulthood. This generation of children and adolescents must deal with a number of different psychosocial, behavioral, and medical issues. Our aim is to discuss these issues that affect PHIV youth in the United States in greater detail. First, we will discuss the social and behavioral aspects of perinatal HIV infection, including effects on mental health, the potential for substance abuse, and the challenges involved in transitioning from the pediatric to the adult healthcare system. Next, we will delve into the reproductive choices, contraceptive practices, parenting intentions, and tendencies to disclose HIV status to potential partners. Lastly, we will describe obstetrical outcomes of these PHIV-infected adolescents and young adults. Throughout the article, we will highlight issues that are important for physicians caring for these patients, as well as areas where further studies are needed.