Polymers, macromolecules in nature and bio-polymers like proteins and antibodies are present in our every-day life and play an important role in our economy. They are obviously present as plastic products (e.g., containers, clothing, car tires) or components, e.g., as expedients in pharmaceutical formulations, additives in food and feed, stabilizers in cosmetics, used in construction materials, ceramics and are key in microchip production. Size-exclusion chromatography is the most important characterization technique for macromolecules. This review covers applications, instrumental setup, step-by-step guides for performing experiments and covers theoretical background as well as troubleshooting and tips and tricks.