•The interindividual variability in response to infection is largely unexplained.•Genome-wide technologies are powerful tools to investigate infections.•GWAS have provided insight into resistance and susceptibility to infection.•GWAS have demonstrated the role of major genes in infectious disease outcomes.•GWAS have increased our insight into immune response and host-pathogen interplay. Over the past few years, genome-wide association studies (GWAS) have been increasingly applied to identify host genetic factors influencing clinical and laboratory traits related to immunity and infection, and to understand the interplay between the host and the microbial genomes. By screening large cohorts of individuals suffering from various infectious diseases, GWAS explored resistance against infection, natural history of the disease, development of life-threatening clinical signs, and innate and adaptive immune responses. These efforts provided fundamental insight on the role of major genes in the interindividual variability in the response to infection and on the mechanisms of the immune response against human pathogens both at the individual and population levels.