Necroptosis, a programmed form of necrotic cell death, is orchestrated by a complex molecular signaling and receptor-interacting protein kinase 3 (RIP3), and mixed lineage kinase domain-like protein (MLKL) plays a crucial role in its execution. It is associated with the loss of cellular integrity and the release of intracellular content. As a result of such damaged cells, the immune cells are attracted promoting inflammation and further harmful environment. Because necroptosis mechanisms, at least some of them, are linked with the disruption in redox homeostasis, oxidative stress (OS) seems to be another important player in this cell-damaging event. Several pro-oxidative mechanisms have been suggested to promote necroptosis, while the facilitation of autophosphorylation of RIP1 and RIP3 has been proposed to be the most relevant for the final cytotoxic action of MLKL. Contradictory, pharmacological interventions and nutrients targeting OS might be able to retard necroptosis and prevent tissue damage, for instance, by stabilizing the key necroptotic proteins, controlling the expression of pro-death regulatory genes, etc. In this book chapter, we introduce necroptosis and its molecular mechanisms and discuss possible cellular events that might amplify necroptosis execution due to ongoing OS. Lastly, we provide evidence about the interference of some vitamins and minerals in necroptosis signaling.