The retroviral life cycle requires that significant amounts of RNA remain unspliced and perform several functions in the cytoplasm. Thus, the full-length RNA serves both the viral genetic material that will be encapsulated in viral particles and the mRNA encoding structural and enzymatic proteins required for viral replication. Simple retroviruses produce one single-spliced env RNA from the full-length precursor RNA, whereas complex retroviruses, such as HIV, are characterized by the production of multiple-spliced RNA species. In this review we will summarize the current acknowledge about the HIV-1 alternative splicing mechanism and will describe how this malleable process can help further understanding of infection, spread and dissemination through splicing regulation. Such studies coupled with the testing of splicing inhibitors should help the development of new therapeutic antiviral agents.