Impairment of the mitochondrial electron transport chain has been suggested to be a critical factor in the neuropathogenesis of Parkinson's disease (PD), as inhibition of mitochondrial complex I (CI) activity is consistently detected in PD patients as well as in mitochondrial toxin models of the disorder. Increased levels of various reactive oxygen and nitrogen species appear to contribute to CI inhibition and mitochondrial dysfunction in PD. Reactive nitrogen species (RNS) such as nitric oxide (NO) and its metabolite peroxynitrite (PN) may inhibit CI activity via several different mechanisms including S-nitrosylation, nitration, and protein thiol formation. Studies using various cell and animal PD models have demonstrated that selective mitochondrial CI inhibition in dopaminergic cells may be due to both NO-mediated S-nitrosylation and nitration of CI sub-units. Strategies to modulate mitochondrial NO levels will therefore likely be a promising approach to enhance mitochondrial function and protect dopaminergic neurons against oxidative or nitrosative insult.