Molecular oxygen deficiency leads to altered cellular metabolism and can dramatically reduce crop productivity. Nearly all crops are negatively affected by lack of oxygen (hypoxia) due to adverse environmental conditions such as excessive rain and soil waterlogging. Extensive efforts to fully understand how plants sense oxygen deficiency and their ability to respond using different strategies are crucial to increase hypoxia tolerance. It was estimated that 57% of crop losses are due to floods [1]. Progress in our understanding has been significant in the last years. This topic deserved more attention from the academic community; therefore, we have compiled a Special Issue including four reviews and thirteen research articles reflecting the advancements made thus far.[...].