The complex changes in intracellular Ca2+ concentration that follow cell stimulation reflect the concerted activities of Ca2+ channels in the plasma membrane and in the membranes of intracellular stores, and the opposing actions of the mechanisms that extrude Ca2+ from the cytosol. Disentangling the roles of each of these processes is hampered by the lack of adequately selective pharmacological tools. In this review, Colin Taylor and Lisa Broad summarize the more serious problems associated with some of the commonly used drugs, and describe specific situations in which the multiple effects of drugs on Ca2(+)-signalling pathways have confused analysis of these pathways.