<p>Size-exclusion chromatography coupled with multi-angle static light scattering (SEC/MALS) is a combined separation and detection technique that is principally used for determining the molar mass of natural and synthetic macromolecules and colloidal suspensions. In this Primer, we examine the equipment, experimental set-up, sample preparation and controls needed for SEC/MALS experiments; how data should be processed; the size and molar mass regimes over which various light scattering models can be applied; and relevant equations needed for understanding the methods or for calculating results. We examine some of the applications of SEC/MALS, including the determination of molar mass averages and distributions, and describe the information that should be provided to ensure experimental reproducibility across laboratories. Both fundamental and instrumental limitations are discussed, along with experimental caveats and recommended workarounds. Finally, we conclude with a brief review of applications, challenges and perspectives and of areas where the so-far untapped potential of SEC/MALS can prove advantageous.</p>