Many salamanders have biphasic life cycles with aquatic larval and terrestrial adult phases. In these species, the transition between phases-metamorphosis-requires thyroid hormone (TH) activation of transcriptional programs that cause regression of larval traits and development of adult traits. During salamander evolution, TH signaling pathways have been altered in biphasic species to yield paedomorphic salamanders that retain larval traits and attain sexual maturity in larval aquatic habitats. We review literature concerning the ecology, evolution, and hormonal regulation of metamorphic, paedomorphic, and facultative salamander life histories. We then discuss recent microarray results that detail gene expression signatures of metamorphosis and paedomorphosis, and genetic results that establish TH responsiveness as a continuous trait with a quantitative trait locus (QTL) basis. TH-responsive QTL from ambystomatid salamanders explain variation in metamorphic timing, expression of metamorphosis versus paedomorphosis, and adult fitness traits. We propose a model for salamander life history evolution that links adaptation to aquatic habitats with TH-responsive loci that pleiotropically alter metamorphic timing and adult body size. Future studies that adopt genetic and genomic approaches will further establish salamanders as ideal models for investigating TH signaling mechanisms that regulate postembryonic development and the expression of alternate life histories.