Active compounds derived from Chinese medicines (CMs) have already illustrated immense therapeutic potential over an array of different diseases, and served as an inexhausted source for drug discovery and development. With the continuous development of the instrumentation’s capabilities as far as detection and separation is concerned, analytical methods for these components have come into the spotlight. Based on the extra sensitivity, specificity, and good separation in complex samples, HPLC and LC–MS have been the ultimate tool in the qualitative and quantitative tools for the determination of different types of chemical compounds. Herein, we focus on the achievements in qualitative and quantitative analysis of the major classes of phytochemicals (flavonoids, alkaloids, saponins, terpenoids, and carbohydrates) in CMs through HPLC and LC–MS.