Programmed cell deaths (PCD), including apoptosis, autophagy and programmed necrosis, are genetically determined, complex processes in multi-cellular organisms. Problems with the regulation of PCD have been implicated in a number of diseases including myocardial infarction, cancer and autoimmune disease. As a result, the investigation on PCD regulation has stirred considerable interest. In the past decades, many PCD-involved proteins had been identified as being modulated by post-translational mechanisms, including post-translational modification, protein-protein interactions and protein cleavage, which fall precisely within the range of proteomic analysis. Contemporary quantitative proteomics, interactomics, PTMomics, degradomics, chemical proteomics and pharmacoproteomics have been quickly applied in the field of PCD research, and possess the potential to be the driving forces of the field. This review attempts to highlight some of the major achievements in the application of proteomics in PCD research to trigger further thinking and application.