Surface plasmon resonance and biolayer interferometry are two common real-time and label-free assays that quantify binding events by providing kinetic parameters. There is increased interest in using these techniques to characterize whole virus-ligand interactions, as the methods allow for more accurate characterization than that of a viral subunit-ligand interaction. This review aims to summarize and evaluate the uses of these technologies specifically in virus–ligand and virus-like particle–ligand binding cases to guide the field towards studies that apply these robust methods for whole virus-based studies.