Caenorhabditis elegans is a worm that has been extensively studied, and it is today an accepted model in many different biological fields. C. elegans is cheap to maintain, it is transparent, allowing easy localization studies, and it develops from egg to adult in around 4 days. Many mutants, available to the scientific community, have been developed. This has facilitated the study of the role of particular genes in many cellular pathways, which are highly conserved when compared with higher eukaryotes. This review describes the advantages of C. elegans as a laboratory model and the known mechanisms utilized by this worm to fight pathogens. In particular, we describe the strong C. elegans RNAi machinery, which plays an important role in the antiviral response. This has been shown in vitro (C. elegans cell cultures) as well as in vivo (RNAi-deficient strains) utilizing recently described viruses that have the worm as a host. Infections with mammalian viruses have also been achieved using chemical treatment. The role of viral genes involved in pathogenesis has been addressed by evaluating the phenotypes of transgenic strains of C. elegans expressing those genes. Very simple approaches such as feeding the worm with bacteria transformed with viral genes have also been utilized. The advantages and limitations of different approaches are discussed.