Hypoxia is a common phenomenon of solid tumors and plays an important role in tumor proliferation, angiogenesis, invasion, metastasis, energy metabolism, resistance to chemotherapy and radiotherapy.In this paper, two approaches for targeting hypoxia in cancer therapy are reviewed.One is mol. targeted agents targeting HIFs and relative signal pathway and the other is hypoxia-activated prodrugs targeting tumor hypoxic microenvironment.Several example compounds with their design and mechanism are listed and the particular challenges and opportunities for each strategy are also discussed.