Application of hybrid ONIOM, QM/QM and QM/MM theoretical methods to study catalytic reactions involving molecular, nano-sized and supported transition metal catalysts are reviewed. The best strategies for theoretical studies of full size chemical systems (without simplifying structural approximations and avoiding the usage of unreliable small size models) are highlighted. The influence of the steric and electronic effects of ligands, reactants and molecular environment on reactivity of transition metal catalysts is discussed. (C) 2010 Elsevier B.V. All rights reserved.