Liquid chromatography (LC) is considered by many as a mature technique. Nonetheless, LC technology continues to evolve driven by the need for high-throughput and high-resolution analyses. Over the past several years, small particle size packing materials have been introduced by several column manufacturers to enable fast and efficient LC separations. Several examples of pharmaceutical analyses, including impurity profiling of taxanes and atracurium besylate, in-process testing of peptides in injectable dosage form, using sub-2 um column technology are presented in this paper, demonstrating some of the capabilities and limitations of the technology.