Amphibian species around the world are currently becoming endangered or lost at a rate that outstrips other vertebrates—victims of a combination of habitat loss, climate change and susceptibility to emerging infectious disease (Stuart et al. 2004). One of the most devastating such diseases is caused by the chytrid fungus Batrachochytrium dendrobatidis (Bd), which infects hundreds of amphibian species on multiple continents. While Bd itself has been characterized for some time, we still know little about the mechanisms that make it so deadly. In this issue of Molecular Ecology, Rosenblum et al. describe a genomic approach to this question, reporting the results of a genome-wide analysis of the transcriptional response to Bd in the liver, skin and spleen of mountain yellow-legged frogs (Rana mucosa and R. sierrae: Fig. 1) (Rosenblum et al. 2012). Their results indicate that the skin is not only the first, but likely the most important, line of defence in these animals. Strikingly, they describe a surprisingly modest immune response to infection in Rana, a result that may help explain variable Bd susceptibility across populations and species.