Comparative neuroanatomists since Herrick [1914] have been aware of the paradox that the brain of amphibians, especially salamanders, is less complex than one would expect based on their phylogenetic position among the Tetrapoda. Many features of the brain are less differentiated in salamanders than in tetrapod outgroups, including chondrichthyans and bony fishes, and for some brain characters, the salamander brain is even more simple than that of the agnathans. Here, we perform a cladistic analysis on 23 characters of four sensory systems (visual, auditory, lateral line and olfactory) and the brain. Our taxa include myxinoids, lampreys, chondrichthyans, actinopterygians, Latimeria, Neoceratodus and the Iepidosirenid lungfishes, amniotes, frogs, caecilians, salamanders and bolitoglossine salamanders. Of the 23 characters we examined, 19 are most parsimoniously interpreted as secondarily simplified in salamanders from a more complex ancestral state, two characters are equally parsimonious under both hypotheses, one character (well developed ipsilateral retinotectal projections) is more complex in bolitoglossine salamanders than in vertebrates generally, and only one character (migration of neurons in the medial pallium) is most parsimoniously interpreted as retention of the plesiomorphically simple condition. Secondary simplification of the salamander brain appears to result from paedomorphosis, or retention of juvenile or embryonic morphology into adulthood. Paedomorphosis is correlated with an increase in genome size, which in turn is positively correlated with cell size, but negatively correlated with cell proliferation and differentiation rates. Available data suggest that, although increasing genome size and paedomorphosis tend to compromise the function of the salamander brain, compensating mechanisms have evolved that may restore or even enhance brain function.