Children with perinatal HIV infection may present with clinical features of endocrine dysfunction such as growth failure and pubertal delay. Pediatric care providers and pediatric endocrinologists should implement appropriate preventive, screening, and therapeutic strategies to maximize survival and quality of life in these children. Growth and pubertal delay can be exacerbated by a variety of treatable infectious, endocrine, nutritional, and immunological disorders. Timely diagnosis and appropriate treatment of these conditions may lead to improvement or even normalization of growth and puberty. HIV-infected children with advanced disease should undergo periodic growth evaluation, including GH levels, IGF-I, IGF binding protein 3 and androgens, in order to identify subclinical endocrine dysfunction. However, little is known about the association between HIV infection and endocrine dysfunction in children. Highly active antiretroviral therapy may also be associated with endocrine dysfunction with consequences on growth and puberty. Growth retardation and pubertal delay are always seen in children with advanced HIV infection and are often related to the proinflammatory milieu found in advanced AIDS. Growth and pubertal impairment are markers of advanced disease and require proper evaluation. A dysregulation of the hypothalamic-pituitary axis, toxic or allergic drug reactions may play a role in growth and pubertal delay of HIV-infected children. These dysfunctions require careful monitoring, in order to assess metabolic alterations that may be important in regulation of growth among HIV infected children. Better understanding of the mechanisms leading to impairment of growth and puberty in children with perinatal HIV-1 infection might lead to appropriate treatment when required.