In this review we will attempt to summarise the complex and sometimes contradictory effects that mitochondria have on different forms of calcium signalling. Mitochondria can influence Ca 2+ signalling indirectly by changing the concentration of ATP, NAD(P)H, pyruvate and reactive oxygen species — which in turn modulate components of the Ca 2+ signalling machinery i.e. buffering, release from internal stores, influx from the extracellular solution, uptake into cellular organelles and extrusion by plasma membrane Ca 2+ pumps. Mitochondria can directly influence the calcium concentration in the cytosol of the cell by importing Ca 2+ via the mitochondrial Ca 2+ uniporter or transporting Ca 2+ from the interior of the organelle into the cytosol by means of Na + /Ca 2+ or H + /Ca 2+ exchangers. Considerable progress in understanding the relationship between Ca 2+ signalling cascades and mitochondrial physiology has been accumulated over the last few years due to the development of more advanced optical techniques and electrophysiological approaches.