Analysis of biopharmaceuticals is very complex. It requires a suite of analytical methods and state-of-the-art instruments with maximal resolving power. 2D-LC provides high chromatographic selectivity and resolving power by combining complementary separation modes and enabling direct coupling to mass spectrometers. Future development of 2D-LC-MS will further simplify the instrumentation, method development, and data analysis. This will enable the implementation of the technique in the QA/QC environment. Finally, it is likely that 2D-LC-UV will be used in both R&D and QA/QC groups when analytes have been thoroughly characterized and UV detection is sufficient for quality control purposes.