N-Oxide-containing compounds have been developed as prodrugs that are selectively bioactivated in the hypoxic cells in tumors. This selectivity is based on the net reduction of the N-oxide moiety in the absence of oxygen, in a one or two-electron process, by reductive enzymes. A wide range of N-oxides have been studied and some of them are currently in clinical use. This review covers the principal families of compounds under study and in clinical trials.