The correct regulation of apoptosis is crucial to metazoan development and physiology: too much or too little underlies many diseases. The knowledge that dysregulated cell death is a pathological feature of sickness, however, does not reveal any of the accompanying genetic requirements. In Caenorhanditis elegans, CED-4/Apaf-1 induces apoptosis through CED-3 caspase activation and ICD-1/βNAC represses this death independently of CED-3. To identify additional ced-3-independent suppressors that function similarly to icd-1, we employed feeding strain RNA interference (RNAi) in ced-3 adults and counted extra apoptotic corpses in progeny embryos. 1,714 RNAi targets yielded 3 L novel and significant suppressors mostly involved in mitochondrial, lysosomal, mRNA processing and proteasomal physiology. Some of the mutants exhibited increased cell death in distinct locations and tissue types. Further, analysis in ced-4 and wild type animals partitioned the suppressors into five epistatic classes including mutants that are strongly ced-4-independent. The apoptotic suppressors represent a genome-wide network of apoptotic suppression with potentially conserved apoptotic roles in 24 human disorders. This study establishes the inclusive requirements for preventing apoptosis in a cell and its broad relevance to disease.