The search for new pharmacologically active agents obtained by screening natural sources such as microbial fermentations and plant extracts has led to the discovery of many clinically useful drugs that play a major role in the treatment of human diseases. A recent review pointed out that approximately 60% of the antitumor and antiinfective agents that are commercially available or in late stages of clinical trials today are of natural product origin.1 Historically, the majority of the natural product-based drugs including cyclosporine, paclitaxel, and camptothecin derivatives were first discovered by traditional cell-based in vitro assays (antibacterial, antifungal, antiviral, antiparasitic, or cytotoxic assays) before their real molecular biological targets were identified. These cellular biological responses of natural products are most probably associated with inherent properties of secondary metabolites for the defense of their producing organisms (e.g., fungus against bacteria: β-lactams; fungus against other fungi: echinocandin; agents acting at the cell cycle to inhibit the proliferation of foreign organisms: bryostatin).2 Thus, most traditional cell-based in vitro assays can be viewed as detection methods of the fundamental and unique phenomena of living organisms. As a result, antiinfective and antitumor targets have been, historically, the effective research area for natural products screening programs. Today, with the advent of genomics research and newer molecular biology tools for developing bioassays, more sophisticated biological assays in addition to cell-based assays are being employed routinely in the drug discovery paradigm. Consequently, in recent years a notable number of natural product-derived agents, such as pravastatin, lovastatin, and FK-506, has been discovered by employing mechanism-based screening approaches involving cellular or biochemical targets in their assay design. In addition, a large number of natural products, especially plant-derived drugs, continues to be discovered on the basis of traditional or empirical local medical practices.3 Over the years, however, interest in the pharmaceutical industry in natural products research has been a somewhat cyclical phenomenon. Most recently, as the lead compound generation and drug discovery processes have been significantly impacted by emerging approaches such as advanced genomics, high-throughput screening, combinatorial chemistry and biology, and computer-assisted de novo drug design, there is an emerging perception that chemical diversity, especially among small organic molecules, may no longer be in short supply, and thus, the role that natural products have played historically in lead generation may start to diminish. This review is intended to summarize, mostly from the perspective of pharmaceutical industry, a number of important natural product-based drug developments in the past 10-15 years, which have led to therapeutically useful agents either in current clinical use or in various stages of clinical trial. It is hoped that this review will be able to address the recent contributions of natural products research to overall drug discovery and development and the role that this field will play in future. The discussion that follows is divided into five major disease areas with brief examples of interesting natural product molecules provided for each.