In Nature, calcium carbonate biomineralizations are the most abundant mineralized structures of biological origin. Because many exhibit remarkable characteristics, several attempts have been made to use them as substitution materials for bone reconstruction or as models for generating biomimetic composites that exhibit tailored properties. CaCO3 biomineralizations contain small amounts of amalgamate of proteins and polysaccharides that are secreted during the calcification process. They contribute to control the morphology of the crystallites and to spatially organize them in well-defined microstructures. These macromolecules, collectively defined as the skeletal matrix, have been the focus of a large number of studies aiming at synthesizing in vitro 'biomimetic' materials, according to a bottom-up approach. However, recent proteomic investigations performed on the organic matrices associated to mollusc shells or to coral skeletons have quashed our hopes to generate, with only few 'macromolecular ingredients', biomimetic materials with properties approaching to those of natural biominerals. As a mean value, each matrix comprises a minimum of few tens of different proteins that seem to be strictly associated to calcium carbonate biominerals. Among the proteins that are currently detected, one finds RLCDs-containing proteins (Repetitive-Low-Complexity Domains), enzymes, proteins with protease inhibitors domains and at last, proteins that contains typical ECM (ExtraCellular Matrix) domains. Today, we still do not understand how the skeletal matrix works, and unveiling its complex functioning is one of the challenges for the coming decade, both from fundamental and applied viewpoints. Is it realistic to attempt generating 'abiotically', in a test tube at room temperature, biomimetic composites that mimic natural biomineralizations in their properties? If so, and by supposing that we know the individual functions of all the components of the matrix, is there a minimal number of proteins required for producing in vitro calcium carbonate biomaterials that 'approximate' natural biominerals? These issues are of importance for the future research directions in biomaterials science.