The molecular mechanisms involved in host-microbe interactions during the initial stages of infection are poorly understood. The bacteria-eating nematode Caenorhabditis elegans provides an opportunity to dissect host-microbe interactions in the context of the whole organism, using powerful genomic, genetic and cell-biological tools. Because of the evolutionary conservation of ancient innate host defences and bacterial virulence mechanisms, studies in C. elegans hold great promise to shed light on defences in higher organisms, including mammals. Additionally, C. elegans pathogenesis models provide a platform for the identification of novel classes of anti-infective compounds with therapeutic value.