The vertebrate gastrointestinal tract is a flexible system that can individually be modified to account for changes in amount and quality of food as well as changes in internal demands. In this paper, I summarise some recent findings and ideas about processes on the level of tissues and cells that allow vertebrates to adjust their intestines to fluctuating conditions. In mammals and birds intestinal flexibility is based on a balance of cell proliferation and cell loss. Maintenance as well as up- and down-regulation of the mucosa involves bio-production or dystrophy of tissue. Both are assumed to be energetically expensive. In contrast, up- and down-regulation of the mucosal epithelium of ectotherm sauropsids is based on configuration changes of the pseudostratified mucosal epithelium. Up-regulation of the mucosa size does not involve cell proliferation, thus it is presumably an energetically cheap process. A comparison of mammals, birds, and ectotherm sauropsids (mainly snakes) allows the development of some new ideas about the historical path of the evolution of gastrointestinal flexibility. Snakes seem to share with other basal tetrapods a phylogenetically plesiomorphic pattern. Birds and mammals have independently evolved new mechanisms that sustain flexibility at a high metabolic level.