Programmed cell death is critical for maintenance cellular organisms homeostasis. Necroptosis is a recently identified mode of programmed cell death that morphologically similar to necrosis. Necroptosis is mediated by Receptor-interacting serine/threonine-protein kinase 3 (RIPK3) and its substrate Mixed lineage kinase domain-like protein（MLKL）. It has been shown that necroptosis is related to several human diseases, such as inflammatory diseases, autoimmune diseases, tumors and degenerative diseases. In this review, we will discuss the molecular mechanisms of necroptosis and its associated diseases.