Calcification of glutaraldehyde-treated porcine tissue heart valves (xenografts) is not a unique phenomenon but characteristic of a variety of synthetic elastomers and to a lesser extent of non-elastomeric polymers. The main commonality between them is their relative flexibility, permeability, and porosity, and differing capability to adsorb and to absorb various blood components. Although the possibility of biochemical factors involving calcium homeostasis and vitamin K-dependent protein carboxylation as recently proposed by others should not be ignored, it should be noted that calcification of synthetic elastomers has been reported with or without continuous anticoagulation with coumarin derivatives. This paper presents a physico-chemical view showing that despite the observed calcifications with a small number of xenograft valves, their otherwise impressive performance in the physiological environment is due to a significant extent to thermodynamic, molecular and supramolecular factors. The longevity of glutaraldehyde-treated tissue valves can be further improved by special methods. Calcification is especially characteristic for flexing and otherwise moving and pulsating surfaces, typical of many experimental circulatory assist devices and artificial hearts intended for long-term uses.