Amphibian populations are declining at an unprecedented rate worldwide. A number of declines have been linked to a pathogenic skin fungus, Batrachochytrium dendrobatidis. Although amphibians have robust immune defenses, many species seem to be very susceptible to infection by this fungus and to development of the lethal disease called chytridiomycosis. One species that is relatively resistant to B. dendrobatidis is Xenopus laevis. Because X. laevis has been used as a model for studies of immunity in amphibians and because it is relatively resistant to chytridiomycosis, it is a good model to examine immune defenses against B. dendrobatidis. Although much less is known about immune defenses in Bufo boreas, it serves as a second model species because it is very susceptible to B. dendrobatidis. Here we review what is known about innate antimicrobial peptide defenses in the skin and the development of immune responses following experimental immunization with heat-killed fungal cells. Development of an immunization protocol in X. laevis that induces effective defenses may suggest better strategies for protecting vulnerable species such as B. boreas.