The last few months have seen a rush of key papers for the understanding of the role of innate immunity – and in particular of interferon lambda (encoded by IL28B). Three papers by Ge D et al (Nature 2009 Sep; 461:399-401), Tanaka Y et al (Nat Genet 2009 Oct; 41:1105-9) and Suppiah V et al (Nat Genet 2009 Oct; 41:1100-4) identified the role of this gene through genome wide association studies. Thomas DL et al (Nature 2009 Oct; 461:798-801) extended the observation on the importance of the lead single nucleotide genetic to natural clearance of HCV. Rauch A et al. (Gastroenterology 2010 [epub ahead of print]) showed in a genome-wide analysis the unique importance of IL28B in spontaneous clearance, and extended the findings to the HIV/HCV co-infected population. These papers underscored the major role of genetic variation of this locus in disease and treatment response, thus opening a door to new insights in pathogenesis. The studies also solved the riddle of the differences in rates of spontaneous clearance across populations: the frequency of the protective allele parallels the rates of spontaneous clearance across the globe.