Ab initio quantum mechanical calculations are valuable tools for interpretation and elucidation of elemental processes in biochemical systems. With the ab initio approach one can calculate data that sometimes are difficult to obtain by experimental techniques. The most popular computational theoretical methods include the Hartree‐Fock method as well as some lower‐level variational and perturbational post‐Hartree Fock approaches which allow to predict molecular structures and to calculate spectral properties. We have been involved in a number of joined theoretical and experimental studies in the past and some examples of these studies are given in this presentation. The systems chosen cover a wide variety of simple biomolecules, such as precursors of nucleic acids, double‐proton transferring molecules, and simple systems involved in processes related to first stages of substrate‐enzyme interactions. In particular, examples of some ab initio calculations used in the assignment of IR spectra of matrix isolated pyrimidine nucleic bases are shown. Some radiation‐induced transformations in model chromophores are also presented. Lastly, we demonstrate how the ab‐initio approach can be used to determine the initial several steps of the molecular mechanism of thymidylate synthase inhibition by dUMP analogues.