Three questions are crucial to unravel the radiation chemistry of any solid-state molecular system: what is the structure of the radicals formed, how are they formed and why? Molecular modeling methods based on Density Functional Theory – in confrontation with experimental Electron Paramagnetic Resonance (EPR) results – can help in finding an answer to all three questions. In this contri-bution, one view on how to perform such computational research is presented, with emphasis on the application of a periodic approach to biomolecules such as amino acids and carbohydrates. General strategies are outlined and common pit-falls are indicated. Topics include: effect of level of theory, model space and tem-perature on calculated EPR properties, formation mechanisms of radiation-induced radicals, and reaction path simulations for radiochemical transformations. In three case studies, these principles are applied to several radiation-induced radi-cals of sucrose.