Coccolithophore biominerals, the coccoliths, represent an important part of the Meso-Cenozoic sedimentary archive. Geochemical analyses of coccoliths can be used to unravel climatic fluctuations in the oceanic realm, but such reconstructions are complicated due to the problem of the “vital effect”. This concept refers to the modulation in the record of the physico-chemistry of seawater in calcite due to algal physiology. For decades, it was thought that the magnitude of the vital effect was species-specific and constant for a given species. Recent studies aiming at a mechanistic understanding of these processes point towards a plastic and environmental-dependent interplay between the physiology of coccolithophores and isotopic composition in coccolith calcite. This “mobilis in mobili” relationship opens the door to the possibility to explore the vital effects as palaeoenvironmental proxies undertaking an interspecies approach. New physiological parameters, such as the quantification of calcification rates, pH, and calcium and carbon pools in the coccolith vesicle would further help geologists to constrain the vital effect. Emerging “non-traditional” isotope systems will also contribute to refine the transfer functions between coccolith geochemistry, vital effect, and palaeoenvironments.