Human gamma retrovirus XMRV (xenotropic murine leukemia-related virus) was originally discovered in a subset of prostate cancers linked to an ineffective ribonuclease L (RNaseL)-mediated antiviral pathway (Urisman, et al. PLoS Pathog. 2006;2:e25). Surprisingly, the recent discovery of infectious XMRV in peripheral blood of a majority of chronic fatigue syndrome (CFS) patients (Lombardi, et al. Science. 2009;326:585-9) confirms and extends the clinical relevance of this third pathogenic human retrovirus, in addition to HTLV-1 (delta retrovirus) and HIV (lentivirus).