Ferroptosis is a form of regulated cell death characterized by iron-dependent overaccumulation of lipid peroxides, which causes membrane damage and cell lysis. Ferroptosis can be prevented by cellular antioxidant mechanisms such as glutathione peroxidase 4 (GPX4)-mediated elimination of the lipid peroxides at the cost of glutathione (GSH). As the rate-limiting step of GSH synthesis, the availability of intracellular cystine is controlled by the cell membranelocated cystine/glutamate antiporter system x_c^-. Indeed, the initially identified small molecule inducers of ferroptosis, RSL3 and erastin, turned out to be inhibitors of GPX4 and system x_c^-, respectively.