The redox environment of the cell is currently thought to be extremely important to control cell growth, differentiation, and apoptosis as many redox-sensitive proteins characterize these networks. A recent, widely accepted theory is that free radicals are not only dangerous species but, at low concentration, they have been designed by evolution to participate in the maintenance of cellular redox (reduction/oxidation) homeostasis. This notion derives from the evidence that cells constantly generate free radicals both as waste products of aerobic metabolism and in response to a large variety of stimuli. Free radicals, once produced, provoked cellular responses (redox regulation) against oxidative stress transducing the signals to maintain the cellular redox balance. Growing evidence suggests that in many instances the production of radical species is tightly regulated and their downstream targets are very specific, indicating that reactive oxygen species and reactive nitrogen species actively participate in several cell-signalling pathways as physiological "second messengers." In this review, we provide a general overview and novel insights into the redox-dependent pathways involved in programmed cell death.