In an effort to speed the rate of discovery in space biology and medicine NASA introduced the now defunct model specimen program. Four nations applied this approach with C. elegans in the ICE-FIRST experiment. Here we review the standardized culturing as well as the investigation of muscle adaptation, space biology radiation, and gene expression in response to spaceflight. Muscle studies demonstrated that decreased expression of myogenic transcription factors underlie the decreased expression of myosin seen in flight, a response that would appear to be evolutionarily conserved. Radiation studies demonstrated that radiation damaged cells should be able to be removed via apoptosis in flight, and that C. elegans can be employed as a biological accumulating dosimeter. Lastly, ICE-FIRST gave us our first glimpse at the genomic response to spaceflight, suggesting that altered Insulin and/or TGF-beta signaling in-flight may underlie many of the biological changes seen in response to spaceflight. The fact that the results obtained with C. elegans appear to have strong similarities in human beings suggests that not only will C. elegans prove an invaluable model for understanding the fundamental biological changes seen during spaceflight but that it may also be invaluable for understanding those changes associated with human health concerns in space.