Recent formal developments and applications of the 'freeze-and-conquer' strategy proposed by Wesolowski and Warshel in 1993 to study large systems at quantum mechanical level are reviewed. This universal approach based on density functional theory allows one to link, via the orbital-free embedding potential, two parts of a larger system described at different levels of accuracy leading thus to significant savings in computational costs. As a result, applicability of conventional methods of quantum chemistry can be extended to even larger systems. It is shown that the 'freeze-and-thaw' approach applying the first-principles based approximation to the orbital-free embedding potential recently developed in our group provides a powerful and universal technique to study such embedded molecules (or molecular complexes), which are not linked with their microscopic environment by covalent bonds.