A liquid chromatographic fingerprinting methodology has been established for identification and quality control of traditional herbal medicines. The methodology was developed from four case studies. Samples of Herba Artemisia annua, Herba Artemisia scoparia, Rhizoma Ligusticum chuanxiong (also called Rhizoma chuanxiong), and Rhizoma Ligusticum jeholense (also called Rhizoma ligustici) were investigated. In each case study, sample preparation and chromatographic conditions (column, organic modifier, column temperature, detection wavelength, and mechanism) were varied to obtain good fingerprints, i.e. with the maximum number of peaks. Further optimization was then performed either by reducing the analysis time or increasing efficiency. The case studies led to the development of a general methodology consisting of sample preparation and HPLC fingerprint development. The fingerprints obtained with the developed methodology were then successfully used to distinguish between the two Artemisia species and between the two Ligusticum species. The methodology also was used to obtain fingerprints for a large number of different Vietnamese Mallotus species, and for Citri reticulatae pericarpium samples collected in different regions of China.