This article describes high-performance liquid chromatography and ultra-high-performance liquid chromatography that are used to separate and quantify the chemical components in any sample that can be dissolved in a liquid. This includes pharmaceutical drugs, medicinal plant extracts, food constituents, flavors, fragrances, industrial chemicals, pesticides, and pollutants. Readers are introduced to the most commonly employed mode, reverse-phase chromatography, with examples and an exclusive focus on commercially available instruments and consumables. The discussion covers the various processes involved in liquid chromatography, including assessing a separation of sample components, adjusting the mobile phase, choosing the stationary phase, optimizing a separation, preparing real samples, and analyzing complex samples.