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A fresh examination of the past successes of natural products as medicines and their new future from both conventional and new technologies. High-performance liquid chromatography profiling, combinatorial synthesis, genomics, proteomics, DNA shuffling, bioinformatics, and genetic manipulation all now make it possible to rapidly evaluate the activities of extracts as well as purified components derived from microbes, plants, and marine organisms. The authors apply these methods to new natural product drug discoveries, to microbial diversity, to specific groups of products (Chinese herbal drugs, antitumor drugs from microbes and plants, terpenoids, and arsenic compounds), and to specific sources (the sea, rainforest, and endophytes). These new opportunities show how research and development trends in the pharmaceutical industry can advance to include both synthetic compounds and natural products, and how this paradigm shift can be more productive and efficacious.