Retroviruses, such as HIV-1, are enveloped RNA viruses that use the enzyme reverse transcriptase (RT) to make a DNA copy of their RNA genome during replication in the host cell. The retrovirus life cycle is generally divided into two distinct phases: the early and late phase. The early phase encompasses virion entry into the host cell, reverse transcription of the viral RNA, nuclear import of the pre-integration complex (PIC), and integration of viral DNA into the host chromosome. The late phase involves transcription of viral DNA to multiple copies of viral RNA, translation of viral proteins, trafficking of viral proteins and genome to assembly sites, budding of viral particles, and, finally, maturation. A number of host factors have been implicated in specific steps of virus replication, and identification of such factors is a rapidly growing field. Recently, many host proteins were identified in genome-wide siRNA screens as being required for HIV-1 replication [1–3].