Genetically programmed cell death is a universal and fundamental cellular process.Apoptosis and necrosis are two common features of programmed cell death that play vital roles in development and maintaining homeostasis in metazoans.Dysfunction of the regulated machinery may lead to carcinogenesis or autoimmune diseases.On the other hand, inappropriate death of essential cells may also lead to organ dysfunction or even death, such as ischemia-reperfusion injury and neurodegenerative disorders.Our laboratory has been using bioactive small molecules (either natural products or non-natural compounds)in a genetic-like approach to probe fundamental biological processes like programmed cell death.Herein, we would like to report our recent research progress on the development of small molecule probes to dissecting programmed cell death.In this respect, novel small molecule modulators of programmed cell death may pave the way for the development of potentially therapeutic treatment for the related intractable human diseases.