Discovered as an important part of the phagocytic process, NADPH oxidases (NOX) are a family of enzymes which are distributed in the majority of tissues including brain cells. In neurons and glia, NOXs play an important physiological role in signal transduction and redox homeostasis. However, activation of NOX in some conditions including ischemia/reperfusion, excitotoxicity (defined as neuronal injury and death resulting from prolonged glutamate exposure) and inflammation can be a source for overproduction of reactive oxygen species (ROS) and induction of oxidative stress. Activation of NOX and oxidative stress is shown to be one of the major triggers for neuronal death in the pathogenesis of most neurodegenerative disorders including Parkinson’s disease. Here we review the role of NOXs in the mechanism of neurodegeneration of Parkinson’s disease, discuss possible triggers of NOX in this pathology and possible strategies for neuroprotection based on the inhibition of NOX.