Acquired immunodeficiency syndrome (AIDS) is a viral disease caused by human immunodeficiency virus type-1 (HIV-1) and type-2 (HIV-2). Both of these are retroviruses. In vivo models discuss nonhuman primate models for AIDS. Animals can be utilized for understanding the hitherto unknown aspects about AIDS or for preclinical evaluation of potential antiretroviral compounds and vaccine strategies. Pigtailed macaques develop lymphadenopathy and rash over the abdominal and inguinal regions; HIV DNA can be detected in PBMC and seroconversion is observed in these animals. Because of similarity of disease progression in the humans and baboons, it is possible to study pathogenesis of AIDS in baboons including the immunobiology of viral latency, mechanisms of disease progression, the lymphatic tissue pathogenesis, the dynamics of viralhost interactions, the acquired immune response and also the modes of transmission of HIV. Severe combined immunodeficiency (SCID) mice models are discussed. These mice have an autosomal recessive mutation that impairs the rearrangement of B and T-cell receptor genes and thus immunocompetency of these animals. Human-cord blood leukocyte–neonatal SCID are developed to mimic paediatric HIV infection. These mice are constructed by intraperitoneally injecting human cord blood leukocytes (hu-CBL) into 1–4 day old neonatal C. B-17 scid or scid mice. Transgenic mice models are described. The disease is characterized with thymic atrophy, depletion of CD4+ cells, architectural changes in lymphoid organs, wasting and failure to thrive, diarrhoea, interstitial lymphocytic pneumonitis, tubular interstitial nephritis, and early death. Visna virus is a nononcogenic retrovirus that causes chronic diseases of sheep including pneumonia, neurological diseases, and so on and affects mononuclear cells. The failure of blood-brain barrier (BBB) structural integrity and its functions play a pivotal role in the development of HIV induced CNS destruction. In cultured brain microvascular endothelial cells human endothelial cells are taken from umbilical cord and astrocytes from human cerebrum.