Many experimental techniques, such as isothermal titration calorimetry (ITC), bi-layer interferometry (BLI), and nuclear magnetic resonance (NMR), have been used to provide key insights into protein-small molecule binding. NMR, in particular, has been useful in evaluating the energetics of carbohydrate aromatic interactions. However, the use of these experimental techniques is limited by the time required to produce each candidate system, the low binding affinities of the candidate interactions, and the inability to probe and compare specific interaction orientations. Alternatively, computational first-principles methods, including density functional theory (DFT) and symmetry-adapted perturbation theory (SAPT) enable rapid energetic assessments of numerous instances of intermolecular interactions from many distinct biological systems. While limited by the approximations inherent to the electronic structure methods used, the difficulty of computing entropic differences, and the effects of the full, solvated protein environment, these methods are essential tools in the analysis of carbohydrate aromatic interactions.