There is emerging consensus that oxidative stress play a paramount role in the molecular toxicity of both METH and MDMA. Free radicals can arise secondary to oxidative deamination of monoamines, cathecolamines autoxidation, hypothermia, lipoperoxidation and even cellular death. There is very little doubt that the toxic effects of METH and MDMA are mediated either by the direct effect of METH and MDMA or by its redox active metabolites. Metabolites formed in liver cells can reach the others organs (heart, kidney, brain, etc) and produce their own toxic effects inducing cellular oxidative stress and lipoperoxidation. The present review is aimed to further clarify the mechanisms of METH and MDMA-induced toxicity, mainly focusing on the role of oxidative stress pathway.