Programmed cell death (PCD) is a physiological process occurring during development and in pathological conditions of animals and plants. The cell death program can be subdivided into three functionally different phases: a stimulus-dependent induction phase, an effector phase during which the wide range of death-stimuli are translated to a central coordinator, and a degradation phase during which the alterations commonly considered to define PCD (apoptotic morphology of the nucleus and chromatin fragmentation) become apparent. Recent studies suggest that mitochondrial permeability transition is the central coordinator of PCD and deciding whether or not a cell will die. There is increasing evidence that reactive oxygen intermediates (ROI) serve as direct and indirect mediators of PCD in mammalian and plant cells. Overexpression of genes encoding pro- and antioxidant enzymes in transgenic animals and plants has been informative regarding the function of ROI. Recent data imply a dual role of ROI in the apoptotic process: first, as a facultative signal during the induction phase, and, second, as a common consequence of mitochondrial permeability transition leading to the final destruction of the cell. The present review discusses and compares new insights into the function of ROI during PCD in mammalian cells and in human and plant diseases.