Lungless salamanders (family Plethodontidae) are classic models of reproductive behavior and mating. Male and female salamanders perform stereotyped courtship behaviors that culminate in external sperm transfer for internal fertilization, and such behaviors include the “tail straddling walk” that has persisted for ~130 million years of salamander evolution. In the majority of plethodontid species, male salamanders deliver non-volatile protein courtship pheromones that modulate female mating behavior. These pheromones have been co-opted from numerous gene families and experienced rapid evolution, presumably in response to coevolutionary pressures from female receptors. Three pheromone types have been chemically purified and experimentally demonstrated to alter female mating behavior: PRF, PMF, and SPF. Remarkably, recent analysis by quantitative mass spectrometry identified paralogs of all three pheromone families as major sperm proteins that are hypothesized to play essential roles in salamander fertilization. As the most speciose family of salamanders (496 of 766 species), plethodontid salamanders have experienced expansive radiations throughout the North and Central American coasts where many species are divided along ecological gradients (e.g. elevation) with varying levels of hybridization and genetic introgression. Such hybrid zones provide natural experiments to explore how new reproductive barriers – and ultimately speciation – may evolve within homologous proteins found at both pre-mating (pheromone) and post-mating (sperm) molecular interactions.