Nonmammalian model organisms have become a cornerstone of systems biology research. Like the Rosetta Stone, which enabled modern scholars to decode ancient Egyptian hieroglyphics, model organisms enable biologists to decipher the genetic code underlying the complex physiological processes common to all life. C. elegans provides a particularly striking example of the experimental utility of model organisms. Genetic, molecular and systems biological characterization of this organism is greatly facilitated by its short life cycle and high rate reproduction, and by the ease with which it can be cultured in the laboratory. C. elegans also has a fully sequenced and well-annotated genome, which is assembled in readily accessible public databases along with virtually all other biological data on this organism. C. elegans: Methods and Applications aims to enhance the readily available methodologies for the study of C. elegans by providing overviews and concise, step-by-step descriptions of the most state-of-the-art methods currently being utilized in the field. Some of the methods presented include forward and reverse genetic analysis, data mining and comparative genomics strategies, electron and fluorescence microscopy methods, automated imaging methods for worm behavioral analysis, functional genomics strategies, and cutting-edge methods for physiological analyses. This comprehensive collection of methods, written by experts in the field, endeavors to serve as a roadmap for researchers, illustrating the type or research that is possible with C. elegans, and illuminating its potential as a vehicle for future discovery.