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The nematode Caenorhabditis elegans has been a powerful experimental organism for almost half a century. Over the past 10 years, researchers have begun to exploit the power of C. elegans to investigate the biology of a number of human pathogens. This work has uncovered mechanisms of host immunity and pathogen virulence that are analogous to those involved during pathogenesis in humans or other animal hosts, as well as novel immunity mechanisms which appear to be unique to the worm. More recently, these investigations have uncovered details of the natural pathogens of C. elegans, including the description of a novel intracellular microsporidian parasite as well as new nodaviruses, the first identification of viral infections of this nematode. In this review, we consider the application of C. elegans to human infectious disease research, as well as consider the nematode response to these natural …