Apoptosis is an evolutionary conserved homeostatic process involved in distinct physiological processes including organ and tissue morphogenesis, development and senescence. Its deregulation is also known to participate in the etiology of several human diseases including cancer, neurodegenerative and autoimmune disorders. Environmental stressors (cytotoxic agents, pollutants or toxicants) are well known to induce apoptotic cell death and to contribute to a variety of pathological conditions. Oxidative stress seems to be the central element in the regulation of the apoptotic pathways triggered by environmental stressors. In this work, we review the established mechanisms by which oxidative stress and environmental stressors regulate the apoptotic machinery with the aim to underscore the relevance of apoptosis as a component in environmental toxicity and human disease progression.