Human immunodeficiency viruses (HIV) are retroviruses belonging to the primate lentivirus family that consists of at least 11 lineages. Independent zoonotic events of primate lentiviruses crossing into humans resulted in the emergence of HIV-1 and HIV-2. HIV-1 is comprised of four phylogenetic Groups, M (major), N (non-M, non-O), O (outlier) and P, each representing a separate cross-species transmission from primates into humans. HIV-1 Group M is most prevalent and responsible for the global epidemic and is subdivided into 9 subtypes based on sequence heterogeneity. Due to dual or coinfections of subtypes and recombination event between HIV strains, a wide diversity of circulating recombinant forms (CRFs) and unique recombinant forms (URFs) occur worldwide. Genetic divergence, mutations, evolution and the continual global redistribution of HIV continues to pose a significant challenge to the reliability of serology and molecular assays used for diagnosis. Global surveillance program is important for understanding HIV genetic diversity and to ascertain that despite genetic variation, all HIV infections are efficiently diagnosed by serology and molecular assays.