Many studies have shown evidence in support of the beneficial effects of phytochemicals in preventing chronic diseases, including cancer. Among such phytochemicals, sulphur-containing compounds (e.g., isothiocyanates; ITCs) have raised the scientific interest by exerting unique chemo-preventive properties against cancer pathogenesis. ITCs are the major biologically-active compounds capable of mediating the anticancer effect of cruciferous vegetables. Recently, many studies have shown that higher intake of cruciferous vegetables is associated with reduced risk of developing various forms of cancers primarily due to a plurality of effects including i) metabolic activation and detoxification, ii) inflammation, iii) angiogenesis, iv) metastasis and v) regulation of the epigenetic machinery. In the context of human malignant melanoma, a number of studies suggest that ITCs can cause cell cycle growth arrest and also induce apoptosis in human malignant melanoma cells. On such basis, ITCs could serve as promising chemo-therapeutic agents that could be used in the clinical setting to potentiate the efficacy of existing therapies.