The surface of proteins is covered by side chains of polar amino acids that are imperative for modulating protein functionality through the formation non-covalent intermolecular interactions. However, despite their tremendous importance, the unique structures of protein side chains require tailored approaches for investigation by NMR spectroscopy, and so have traditionally been understudied compared to the protein backbone. Here, we review substantial recent methodological advancements within NMR spectroscopy to address this issue. Specifically, we consider advancements that provide new insight into methyl-bearing side chains, show the potential of using non-natural amino acids, and reveal the actions of charged side chains. Combined, the new methods promise unprecedented characterisations of side chains that will further elucidate protein function
