As an important form of programmed cell death, necroptosis is getting more and more attention and has overturned the previous assumption that cell necrosis was not controlled by signaling pathway. Necroptosis plays a role in initiation and development of many diseases, including inflammatory diseases, cardiovascular diseases and neurological diseases. Furthermore, research proved that inducing necroptosis of tumor cells could inhibit tumor cell growth or promote tumor cell death, which is a promising strategy to treat neoplasm and overcome drug resistance problem of tumor treatment. Therefore, necroptosis can promote the development of some diseases, and it could be a potential strategy to treat tumor. Inhibiting or inducing necroptosis in different diseases with different treatment strategies is expected to treat many clinical diseases. Therefore, developing necroptotic inducers and inhibitors is of great significance in fields of both scientific research and clinical application. This article reviews the underlying mechanism of necroptosis under different pathophysiological situations and innovatively summarizes therapeutic potentials of inducers and inhibitors related to necroptotic signaling pathways in various diseases.