Ribosomal frameshifting is a mechanism of gene expression used by several RNA viruses to express replicase enzymes. This article focuses on frameshifting in two human pathogens, the retrovirus human immunodeficiency virus type 1 (HIV-1) and the coronavirus responsible for severe acute respiratory syndrome (SARS). The nature of the frameshift signals of HIV-1 and the SARS-CoV will be described and the impact of this knowledge on models of frameshifting will be considered. The role of frameshifting in the replication cycle of the two pathogens and potential antiviral therapies targeting frameshifting will also be discussed.