The transformation of biomass‐derived molecules into platform chemicals that can directly be employed by the chemical industry is one of the challenges in catalysis in this century. While some processes are cost‐effective and industrially available, the molecular insight has been advancing at a slow pace when compared to other areas (like energy conversion). In the present review we describe the main challenges imposed to the theoretical simulations for the study of these complex molecules and how we have addressed the most crucial issues. In particular, we focus on technical aspects like the need for dispersion and solvation contributions and the complexity of reaction networks that requires new approaches and ways to compile the results in the form of databases to allow the study of large reaction networks for the decomposition of C2 alcohols, or the plethora of functional groups of cyclic molecules such as lignin and sugars. Finally, we put forward a few applications showing the potential of atomistic simulations in the field.