The trace elements iron and selenium play decisive roles in a distinct form of necrotic cell death, known as ferroptosis. While iron promotes ferroptosis by contributing to Fenton-type reactions and uncontrolled lipid autoxidation, the hallmark of ferroptosis, selenium in the form of glutathione peroxidase 4 (GPX4), subdues phospholipid peroxidation and associated cell death. Beyond the canonical cystine/glutamate antiporter system x(c)(-)/glutathione/GPX4 nexus, recent studies unveiled the second mainstay in ferroptosis entailing extra-mitechondriai ubiquinone, ferroptosis suppressor protein 1, and NAD(P)H as electron donor. Unlike GPX4, this selenium- and thiol-independent system acts on the level of peroxyl radicals in membranes thereby restraining Hold peroxidation. Therefore, ferroptosis is a multifaceted cell-death paradigm characterized by several metabolic networks, whereby metabolic dyshomeostasis may cause ferroplotic cell death and organ failure. Here, we discuss the basic features of ferroptosis with a focus on selenium, offering exciting opportunities to control diseases linked to ferroptosis, including transient ischemia reperfusion and neurodegeneration.