Plants have long served as traditional herbal medicines, and natural products make excellent leads for new drug development. New plant-derived medicines can come from three sources: single active principles, active fractions, and validated prescriptions. Conventionally, for single active compounds, lead discovery and drug development involve highly efficient bioactivity- directed fractionation and isolation (BDFI) coupled with structural characterization, analog synthesis, and mechanism of action studies. Today, new scientific technologies, including tissue culture and biological screening methods, continue to improve this process. For multi-component herbal prescriptions, standardization and quality control, including GAP (Good Agricultural Practice), GMP (Good Manufacturing Practice) and GCP (Good Clinical Practice), must be performed to guarantee high quality and consistency. In addition, reliable chemical, pharmacological, as well as drug administration, distribution, metabolism, excretion, and toxicological (ADMET) studies are needed to validate herbal efficacy and safety. This talk will discuss the principles listed above, particularly focusing on the successful development of anticancer and anti-HIV clinical trials candidates from numerous bioactive compounds discovered in the author’s Natural Products Laboratory. Continued exploration of under-investigated plant species should guarantee bright prospects for sustained discovery and development of new medicines for this century.