Expression of the integrated HIV-1 provirus is achieved by overcoming multiple barriers to the processing, transport and utilization of the viral RNA. Some of the strategies involve viral encoded proteins (i.e. Rev, Gag). However, in large part it is host factors that play essential roles in the movement of HIV-1 RNA from the site of transcription to its ultimate encapsidation into new virions. Identifying these factors and their mechanism of action provides not only important insights into HIV-1 molecular biology but also that of the cell machinery itself. In this review, we highlight the viral and host factors regulating the splicing, polyadenylation, transport, and translation of HIV-1 RNA. The observations made underline the multiple fate decisions that must be made at each stage of the viral RNA metabolic pathway and highlight potential new avenues for controlling HIV-1 replication.