Although natural products have been marginalized by major pharmaceutical companies over the last 20-30 years, the changing landscape of drug discovery now favors a greatly enhanced role for Nature's privileged structures. Screening for drug leads in phenotypic screens provides the best opportunity to realize the value of natural products. Advances in total synthesis, especially function-oriented syntheses and biosynthetic technologies offer new avenues for the medicinal chemical optimization of biologically active secondary metabolites. Genomic research has given new insights into biosynthetic processes as well as providing evidence that a wealth of unrealized biosynthetic potential remains to be explored. As Pharma strives to develop innovative and highly effective new drugs, natural products will be increasingly valued as sources of novel leads whose further development will be expedited by emerging technologies.