Chemodynamic therapy (CDT) takes the advantages of Fenton-type reactions triggered by endogenous chemical energy to generate highly cytotoxic hydroxyl radicals. As a novel modality for cancer treatment, CDT shows minimal invasiveness and high tumor specificity by responding to the acidic and the highly concentrated hydrogen peroxide microenvironment of tumor. The CDT approach for spatiotemporal controllable reactive oxygen species generation exhibits preferable therapeutic performance and satisfying biosafety. In this review article, we summarized the recent advances of stimuli-activatable nanomedicines for CDT. We also overviewed the strategies for augmenting CDT performance, including increasing the catalytic efficacy through rational design of the nanomaterials, modulating the reaction condition, inputting external energy field, and regulating the tumor microenvironment. Furthermore, we discussed the potential and challenges of stimuli-activatable nanomedicine for clinical translation and future development of CDT. This article is categorized under: Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease Nanotechnology Approaches to Biology > Nanoscale Systems in Biology Diagnostic Tools > In Vivo Nanodiagnostics and Imaging.