Resistance to caspase-dependent apoptosis is often responsible for treatment failures in cancer. Finding novel therapeutic strategies that can activate alternative cell death programs appears to be appealing. Necroptosis is a form of programmed necrosis that occurs under caspase-deficient conditions. This alternative form of cell death has recently emerged as a potential anticancer therapy that could overcome apoptosis resistance. A growing understanding of the molecular events triggering necroptosis helped to examine its implication in cancer development and to define new therapeutic strategies. Genetic and proteomic analysis suggest that necroptosis is deregulated in many cancers. Various preclinical and clinical compounds induced necroptosis and have demonstrated significant therapeutic efficacy. Moreover, accumulating evidence has shown that necroptosis promotes anticancer immune response. A better knowledge of the cascade of events regulating necroptosis is expected to assess the feasibility of its therapeutic exploitation for cancer therapy.