Human immunodeficiency virus requires receptors and cellular factors in target cells in order to complete a successful replication. Conversely, host cells express different proteins like TRIM5a, Tetherin BST-2, as well as cytidine deaminase proteins (APOBEC3) to suppress viral replication. These proteins, known as cellular restriction factors, provide an initial defense against infection as components of the innate immune response. The best characterized restriction factor is the cytidine deaminase APOBEC3G that has been shown to have an important role in HIV pathogenesis. Here, we review the current knowledge of host restriction factors, focusing on APOBEC3G, and possible therapeutic strategies against HIV infection.