Soil flooding and associated hypoxia stress impose major penalties on agricultural crop production. Yet, the progress in crop breeding to flooding stress is significantly handicapped by the complexity of hypoxia signalling and adaptation mechanisms. In this work, we discuss the ionic and molecular mechanisms underlying plant adaptive responses to oxygen deprivation and elucidate the role of the plasma- and organelle-based membrane transporters 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 PCD. The latter process may be of adaptive significance, contributing to aerenchyma formation by a mechanism unrelated to lysogeny. This process can be strongly affected by hypoxia-induced changes in the amino acid pool profile and, specifically, 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.