Influx of calcium into cells following stimulation of cell surface receptors is a key process controlling cellular activity. However, despite intensive research, there is still no consensus on precisely how calcium entry is controlled in electrically non-excitable cells. In particular, the regulation of depletion-activated or 'capacitative' calcium entry continues to be a focus of debate. Work published in the last 2 years has lent new impetus to the so-called 'conformational coupling' theory, although evidence for the existence of soluble messengers between the ER and the plasma membrane also continues to appear. In addition, there remains disagreement on whether intra-store [Ca2+] has to fall below a threshold before Ca2+ entry is activated. A further major question is the identity of the putative depletion-operated Ca2+ channel or channels. Here discussion has largely focussed on whether homologue(s) of the Drosophila TRP ('Transient Receptor Potential') protein is/are the elusive channel, or at least a part of it. Finally, it remains possible that Ca2+ entry mechanisms other than depletion-activated channels may be important in agonist-evoked Ca2+ influx. This commentary summarizes recent developments in the field, and highlights both current debates and critical unsolved questions. © 2001 Harcourt Publishers Ltd.