Several amphibian lineages epitomize the faunal biodiversity crises, with numerous reports of population declines and extinctions worldwide. Predicting how such lineages will cope with environmental changes is an urgent challenge for biologists. A promising framework for this involves mechanistic modeling, which integrates organismal ecophysiological features and ecological models as a means to establish causal and consequential relationships of species with their physical environment. Solid frameworks built for other tetrapods (e.g., lizards) have proved successful in this context, but its extension to amphibians requires care. First, the natural history of amphibians is distinct within tetrapods, for it includes a biphasic life cycle that undergoes major habitat transitions and changes in sensitivity to environmental factors. Second, the accumulated data on amphibian ecophysiology is not nearly as expressive, is heavily biased towards adult lifeforms of few non-tropical lineages, and overlook the importance of hydrothermal relationships. Thus, we argue that critical usage and improvement in the available data is essential for enhancing the power of mechanistic modeling from the physiological ecology of amphibians. We highlight the complexity of ecophysiological variables and the need for understanding the natural history of the group under study and indicate directions deemed crucial to attaining steady progress in this field.