Spatiotemporal Ca 2 + signalling in the cytoplasm is currently understood as an excitation phenomenon by analogy with electrical excitation in the plasma membrane. In many cell types, Ca 2 + waves and Ca 2 + oscillations are mediated by inositol 1,4,5-trisphosphate (IP 3 ) receptor/Ca 2 + channels in the endoplasmic reticulum membrane, with positive feedback between cytosolic Ca 2 + and IP 3 -induced Ca 2 + release creating a regenerative process. Remarkable advances have been made in the past year in the analysis of subcellular Ca 2 + microdomains using confocal microscopy and of Ca 2 + influx pathways that are functionally coupled to IP 3 -induced Ca 2 + release. Ca 2 + signals can be conveyed into the nucleus and mitochondria. Ca 2 + entry from outside the cell allows repetitive Ca 2 + release by providing Ca 2 + to refill the endoplasmic reticulum stores, thus giving rise to frequency-encoded Ca 2 + signals.