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Plants respond to hypoxic stress through either acclimation to the stress or avoidance of it, as they do to most environmental stresses. The hypothesis that has general consensus among the community is that ethylene response factors (ERFs) are central elements that control both types of responses to hypoxia. Recent studies suggest that this may not be the case for all cells experiencing hypoxic stress. Mature maize root cells undergoing hypoxic stress were found to undergo acclimation and avoidance mechanisms involving ERFs, whereas meristematic root cells and cells still undergoing differentiation acclimated to the response without the involvement of ethylene synthesis or ERFs. Phytoglobins (PGBs) and NO were demonstrated to be components critical to the acclimation response. These findings are discussed relative to the possibility that PGBs may be acting as molecular switches controlling cellular stress responses and hormonal changes and responses in cells.