Publisher Summary The chapter discusses that hydrogen peroxide- (H 2 O 2 ) induced apoptosis results in a significant drop in the intracellular pH and superoxide anion (O 2 – ) concentration, irrespective of whether H 2 O 2 is added exogenously or induced intracellularly using drugs. The reduced intracellular milieu then provides an environment permissive for the execution of the death signal. Therefore, it is important to differentiate between oxidative stress, induced by high concentrations of radical oxygen intermediates (ROI) that cause necrosis of the cells, from reductive stress-induced cell death that involves ROI production associated with a drop in the pH i and subsequent activation of the apoptotic cell death pathway. Apoptosis is an active process that involves cross talk among caspase proteases and apoptogenic factors released from the mitochondria. This interaction amplifies the death signal and triggers a cascade of events leading to the acquisition of the apoptotic phenotype via proteolytic degradation of a number of cellular proteins. The chapter refers to the apoptotic signaling triggered by exogenous or endogenous H 2 O2 as “reductive stress-induced apoptosis” as opposed to the oxidative damage induced by necrotic concentrations.