Increased attention has centered on exploiting hypoxia in tumors for targeting the design of selective antitumor agents. This review presents an update of the principal families of compounds under study and in clinical trials, such as N-oxide derivatives, nitro compounds and quinone derivatives. Especially promising for bioreductive activation is the reduction of some moieties able to trigger a mechanism that releases cytotoxic antitumor drugs. The most remarkable redox-activated triggers are presented, N-oxide, nitro, azido, quinone, metal ions, 1,2-benzisoxazolyl and sulfoxide moieties.