The increasing call for an overall picture of the interactions between the components of a biological system that give rise to the observed function is often summarized by the expression systems biology. Both the interpretative and predictive capabilities of holistic models of biochemical systems, however, depend to a large extent on the level of physico-chemical knowledge of the individual molecular interactions making up the network. This review is focused on the structure-based quantitative characterization of protein-protein interactions, ubiquitous in any biochemical pathway. Recently developed, fast and effective computational methods are reviewed, which allow the assessment of kinetic and thermodynamic features of the association-dissociation processes of protein complexes, both in water soluble and membrane environments. The performance and the accuracy of fast and semi-empirical structure-based methods have reached comparable levels with respect to the classical and more elegant molecular simulations. Nevertheless, the broad accessibility and lower computational cost provide the former methods with the advantageous possibility to perform systems-level analyses including extensive in silico mutagenesis screenings and large-scale structural predictions of multiprotein complexes.