Theoretical simulations in the field of heterogeneous catalysis started about two decades ago when the main goal was to understand the activation of small molecules on infinite surfaces. The improvements in the accuracy and the large availability of computers with increasing power have raised the quality of the calculations, the reliability of the results and prompted the interest in their predictions. Such changes have also allowed the study of nanoparticles by the combined investigation of different facets or by taking into account the complete structures. As for the reactivity, theoretical simulations allow the comparison of different synthetic conditions within the same approximation. Consequently, large systematic studies with the same theoretical models can provide databases for properties, structures, prove and disprove hypothetical reaction paths, identify intermediates, and complete the understanding of reaction mechanisms. In some cases, simulations support and give explanations to experiments but new emerging aspects such as the prediction of new properties or the analysis of complex systems are possible. Several challenges are ahead the simulations of reactions on nanoparticles: (i) how to drive the synthesis to achieve the desired architectures and (ii) how to stabilize the active phase under reaction conditions.