With recent progress in active research on flooding and hypoxia/anoxia tolerance in native and agricultural crop plants, vast knowledge has been gained on both individual tolerance mechanisms and the general mechanisms of flooding tolerance in plants. Research on carbohydrate consumption, ethanolic and lactic acid fermentation, and their regulation under stress conditions has been accompanied by investigations on aerenchyma development and the emergence of the radial oxygen loss barrier in some plant species under flooded conditions. The discovery of the oxygen-sensing mechanism in plants and unravelling the intricacies of this mechanism have boosted this very international research effort. Recent studies have highlighted the importance of oxygen availability as a signalling component during plant development. The latest developments in determining actual oxygen concentrations using minute probes and molecular sensors in tissues and even within cells have provided new insights into the intracellular effects of flooding. The information amassed during recent years has been used in the breeding of new flood-tolerant crop cultivars. With the wealth of metabolic, anatomical, and genetic information, novel holistic approaches can be used to enhance crop species and their productivity under increasing stress conditions due to climate change and the subsequent changes in the environment.