NADPH oxidases (Noxs) represent an original pharmacological target because they are the only enzymes whose main function is to produce reactive oxygen species. It is also a double target with the need for stimulation in chronic granulomatosis and inhibition reported in other pathologies (vascular, cancerous, neurological, etc.). The complexity of the involvement of Noxs in pathophysiology has not yet made it possible to obtain a drug that effectively inhibits these enzymes at the clinical level. This issue of the Forum aims to take stock of the obstacles and limitations to the development of these inhibitors both in their preclinical and clinical evaluation.