Biological catalysis is a complex chemical process that involves not only electronic reorganization in the substrate but also the reorganization of the catalyst. This complexity is even larger in the case of post-transcriptional and post-translational modifications which may involve the interaction between two biomacromolecules. However, the development over the past decades of new computational methods and strategies is offering a detailed molecular picture of the catalytic event and a deep understanding of the mechanisms of chemical reactions in biological environments. Here we review the efforts made in the last years to model catalysis in post-transcriptional and post-translational processes. We stress on the advantages and problems of the different computational strategies and their applicability in different cases