For decades marine biologists and earth scientists have wanted to understand how changes in the seawater environment affect coral skeleton growth. That’s because coral calcification builds ecologically important coral reef structures and coral skeletons contain chemical signatures used as recorders of climate. The growth front of the coral skeleton does not come into direct contact with seawater, but instead forms in an extracellular calcifying medium (ECM) controlled by a specialised cell layer called the calcifying ‘calicoblastic’ epithelium. Unravelling the physiology of this calcifying epithelium (and coral physiology in general) is key to understanding why coral calcification responds to environment change. This challenge is an important focus of research at the Centre Scientifique de Monaco (CSM). Using an innovative coral sample preparation in controlled environmental experiments, we carry out in vivo physiological studies using a range of tools including confocal microscopy coupled with physiological indicator dyes and microelectrodes. This research has provided insight into regulation of pH, calcium and dissolved inorganic carbon concentration of the ECM by transcellular transport via the calicoblastic cells. We have also conducted investigations of paracellular transport to better understand how permeability of the calicoblastic epithelium determines exchange of ions and molecules between seawater and the ECM. We also investigate the impact of ocean acidification on these physiological parameters. Overall, our in vivo physiological data complement information arising from ‘omics’ studies on corals at CSM and other laboratories and helps us move towards a clearer understanding of coral calcification in a rapidly changing ocean.