Senescence is a stable cell cycle arrest that can be activated by oncogenic signaling and manifests with changes in cellular organization and gene expression, such as the induction of a complex secretome. Importantly, senescence limits tumor progression and determines the outcome of conventional anticancer therapies. In recent years, therapeutic approaches such as p53 reactivation, inhibition of c-MYC in addicted tumors or treatment with cyclin-dependent kinase (CDK) inhibitors have proven effective by invoking a senescence response. The possibility of using prosenescence therapies for cancer treatment has provoked considerable interest. We propose that the senescence secretome can be a source of novel targets for prosenescence therapies, as it has tumor suppressive actions. Overall, tailored prosenescence therapies have the potential to be used for treating cancer and other pathologies.