This review provides a comprehensive assessment of a previously unexplored topic: elucidating the role that plasma‐ and organelle‐based membrane transporters play in plant‐adaptive responses to flooding. We show that energy availability and metabolic shifts under hypoxia and anoxia are critical in regulating membrane‐transport activity. We illustrate the high tissue and time dependence of this regulation, reveal the molecular identity of transporters involved and discuss the modes of their regulation. We show that both reduced oxygen availability and accumulation of transition metals in flooded roots result in a reduction in the cytosolic K⁺ pool, ultimately determining the cell's fate and transition to programmed cell death (PCD). This process can be strongly affected by hypoxia‐induced changes in the amino acid pool profile and, specifically, ϒ‐amino butyric acid (GABA) accumulation. It is suggested that GABA plays an important regulatory role, allowing plants to proceed with H₂O₂ signalling to activate a cascade of genes that mediate plant adaptation to flooding while at the same time, preventing the cell from entering a ‘suicide program’. We conclude that progress in crop breeding for flooding tolerance can only be achieved by pyramiding the numerous physiological traits that confer efficient energy maintenance, cytosolic ion homeostasis, and reactive oxygen species (ROS) control and detoxification.