Since its commercial introduction in 2004, there has been a considerable interest in ultra-high-performance (pressure) liquid chromatography (UHPLC), which dramatically increases the throughput of regular HPLC methods. Although the ability to achieve fast separations and good resolution are the main drivers for the increasing use of UHPLC, we describe a number of other trends in this review, such as: 1 use of UHPLC technology to perform high-resolution analysis of complex samples; 2 development of columns packed with sub-2-µm particles to achieve different chromatographic modes (i.e. chiral LC, SEC, IEX, HILIC, and SFC); 3 evaluation of higher pressure drop, higher temperature, smaller particle sizes and sub-2-µm core-shell particles, to further improve kinetic performance; 4 use of UHPLC for enhancing the characterization of biopharmaceuticals; and, 5 development of UHPLC-MS for applications, including bioanalysis, multi-residue screening, and metabolomics.