Triggering specific chemical reactions in the disease microenvironment can produce species for disease treatment that have high theranostic performance and low side effects on healthy cells/tissues. Emerging chemoreactive nanomedicine employs nanotechnology to enable the occurrence and/or enhance the rate/efficiency of in situ chemical reactions to satisfy the strict requirements of versatile biomedical applications. This perspective discusses the four essential factors that play roles in the theranostic performance, including nanoreactants, nanoproducts, nanocatalysts and reaction conditions. The design and fabrication principles/strategies for diverse nanosystems and optimization methodologies for reaction conditions in chemoreactive nanomedicine are summarized and discussed alongside the most representative paradigms available. The explored versatile biomedical applications of chemoreactive nanomedicine are clarified, such as tumor therapy, bioimaging, tissue regeneration and antibacterial properties. Finally, this perspective clarifies the difficulties/challenges faced and provides an outlook detailing the future developments/prospects of this intriguing chemoreactive nanomedicine for future clinical translations.