Ferroptosis is an oxidative form of necrotic cell death highly relevant for many degenerative diseases and cancer. Ferroptosis is marked by iron-dependent lipid peroxidation and is distinct from other cell death modalities. Glutathione peroxidase 4 is the key ferroptosis player as it efficiently controls lipid peroxidation. Transgenic mice and animal models of disease have shown which cells and tissues are prone to undergo ferroptosis. The discovery of novel ferroptosis inhibitors and inducers thus offers the great potential in the development of innovative drugs to treat yet incurable diseases.