A study of the effects of imidazolium-based ionic liquids on 60 human cancer cell lines representing diverse histologies has identified four compounds which show potency at a nanomolar dose. Their effects on annexin V, DNA fragmentation, and the cell cycle, together with mitochondrial membrane permeabilization tests, provide insights into their mechanism of action. Also, experiments with A431 human epidermoid carcinoma cells suggest the activation of an apoptotic pathway, due to activity of the initiator caspase 8 and effector caspase 3.