A review of the pharmacological background and clinical activity of different Ca2+ channel blockers concerning reversal of anticancer drug resistance in tumors suggests that verapamil and trifluoperazine may be the most immediate candidates. Reversal of resistance to anthracyclines and vinca alkaloids originally observed in mouse experimental leukemia cell lines has now been extended to other animal cell lines and human tumors as well. Evidence is available that resistance to drugs of other classes such as dactinomycin, etoposide, and mitoxantrone can be reversed by various calcium channel blockers. Apart from enhancing retention of anticancer drugs in tumor cells, little is actually known of the mechanism(s) by which this phenomenon occurs. There is inconclusive evidence for the role of Ca2+ ions and Ca2+ channel receptors in the process, and, furthermore, there is no evidence that Ca2+ channel blocking activity per se is necessary for the reversal of drug resistance.