Increases in cytosolic free Ca²⁺ ([Ca²⁺]_i) represent a ubiquitous signalling mechanism that controls a variety of cellular processes, including proliferation, metabolism and gene transcription, yet under certain conditions increases in intracellular Ca²⁺ are cytotoxic. Thus, in using Ca²⁺ as a messenger, cells walk a tightrope in which [Ca²⁺]_i is strictly maintained within defined boundaries. To adhere to these boundaries and to sustain their modified phenotype, many cancer cells remodel the expression or activity of their Ca²⁺ signalling apparatus. Here, we review the role of Ca²⁺ in promoting cell proliferation and cell death, how these processes are remodelled in cancer and the opportunities this might provide for therapeutic intervention.