Isothiocyanates (ITCs) are breakdown products of glucosinolates contained in cruciciferous vegetables. This heterogeneous family of molecules has the -N=C=S group as its common structural feature and possesses important cytoprotective properties. Their biological interactions are strongly related to modulation of cellular redox status, and a number of studies have documented their indirect antioxidant properties, particularly related to induction of phase-2 enzymes. On the other hand, some direct antioxidant behavior has also been observed for a limited number of ITCs. Paradoxically relevant pro-oxidant properties have also been documented, possibly related to the simultaneous induction of phase-1 enzymes. In this review, we will summarize and discuss the prevailing mechanisms for the antioxidant and pro-oxidant activity of ITCs, both in vivo and in vitro.