As the number of cases and cancer-related deaths are projected to rise in upcoming years, it is urgent to find ways to prevent or treat cancer. As such, food-derived products have gained attention as potential chemopreventive agents due to their availability, safety, and low cost. Isothiocyanates, the breakdown products of sulfur-containing glucosinolates in cruciferous vegetables, have shown substantial anticarcinogenic and chemopreventive activities for different human cancers. Furthermore, organoselenium compounds are known to exhibit chemopreventive and chemotherapeutic activity; moreover, these compounds are more effective anticancer agents than their sulfur isosteres. Hence, isothiocyanates have been modified to yield isoselenocyanates, which are more cytotoxic toward cancer cells when compared to their corresponding sulfur analogues. Herein, the synthesis and development of isoselenocyanates as novel treatments for cancer and other diseases are reviewed, highlighting the diverse chemistry and computational studies of this class of compounds as well as their pertinent biological applications.