Flooding is an environmental stress for many natural and man-made ecosystems worldwide. Genetic diversity in the plant response to flooding includes alterations in architecture, metabolism, and elongation growth associated with a low O(2) escape strategy and an antithetical quiescence scheme that allows endurance of prolonged submergence. Flooding is frequently accompanied with a reduction of cellular O(2) content that is particularly severe when photosynthesis is limited or absent. This necessitates the production of ATP and regeneration of NAD(+) through anaerobic respiration. The examination of gene regulation and function in model systems provides insight into low-O(2)-sensing mechanisms and metabolic adjustments associated with controlled use of carbohydrate and ATP. At the developmental level, plants can escape the low-O(2) stress caused by flooding through multifaceted alterations in cellular and organ structure that promote access to and diffusion of O(2). These processes are driven by phytohormones, including ethylene, gibberellin, and abscisic acid. This exploration of natural variation in strategies that improve O(2) and carbohydrate status during flooding provides valuable resources for the improvement of crop endurance of an environmental adversity that is enhanced by global warming.