Animals exhibit a wide diversity of feeding habits, within which exists a broad continuum of feeding frequencies and feeding patterns. At one end of the continuum are small endotherms that seemingly are continuously digesting to maintain their high metabolic rates, whereas at the opposite end of the spectrum are large ectotherms that as a function of their foraging habits and low energy demands, feed relatively infrequently. In addition, many animals experience each year an extended period of fasting due to the lack of food, harsh conditions, or the conflicting demands of reproduction. Driven by very predictable long episodes of digestive quiescence and the elevated cost of maintaining an active gut, selection would favor the down regulation of GI performance during such fasting periods. Consequently, such an adaptive response would require the capacity to rapidly upregulate GI function with feeding. While such examples of phenotypic flexibility are prevalent across vertebrate taxa, the most striking cases are observed for ectotherms, especially snakes. Studies with snakes have identified a remarkable adaptive interplay between feeding habits and the capacity to regulate intestinal form and function. Species of snakes that feed infrequently in the wild (e.g., pythons, boas, and rattlesnakes) experience with the completion of digestion the downregulation of intestinal hydrolase and transporter activities and atrophy of the intestinal epithelium. Feeding triggers the immediate upregulation of intestinal function and rapid hypertrophy of the epithelium. In contrast, snakes that feed relatively frequently in the wild (i.e., many colubrids) experience only modest regulation of intestinal form and function with feeding and fasting. These snakes, as is the case for many other vertebrates, maintain an active gut between meals. Significant modulation of intestinal structure and function with fasting and feeding have likewise been observed for fishes and amphibians, the latter best exemplified by species that aestivate during dry seasons. The cellular mechanism largely responsible for this dichotomy in intestinal response resides with the extent that the microvilli modulate their surface area. Fasting triggers a rapid shortening of the intestinal microvilli for infrequently feeding snakes, with is reversed with feeding. The 5-fold changes in microvillus length and surface area with fasting and feeding match the magnitude of change of intestinal function. Frequently feeding snakes do not alter microvillus length with feeding, and hence do not experience any significant change in function. Examined for the Burmese python is that feeding triggers a very rapid genomic response; evident by the more than 2000 intestinal genes whose expression are significantly regulated with feeding. A close examination of the adaptive interplay between snake feeding habits and gastrointestinal regulation reveal two caveats, that feeding habits of snakes are highly phylogenetically conserved and that feeding frequency is spread over a broad continuum. Hence, modes of digestive response may be dictated by phylogeny, rather than as adaptations, and species with intermediate feeding habits or that exhibit interpopulation variation in feeding habits, may experience intermediate or alternative mechanisms of digestive response. Preliminary data for boas suggest that feeding habits trumps phylogeny in determining the mode of intestinal response to feasting. Early exploration of the intestinal response of the generalist feeding viperid, the water moccasin (Agkistrodon piscivorus), has found modest regulation of intestinal morphology across populations. Driven by the fitness-based selection of optimizing energy, animals have evolved the integrative machinery to alter gastrointestinal performance based on the periodicity and magnitude of digestive demand.