Many important bioactive compounds have been discovered from natural sources using bioactivity-directed fractionation and isolation (BDFl) [Balunas MJ, Kinghorn AD (2005) Drug discovery from medicinal plants. Life Sci 78:431-441]. Continuing discovery has also been facilitated by the recent development of new bioassay methods. These bioactive compounds are mostly plant secondary metabolites, and many naturally occurring pure compounds have become medicines, dietary supplements, and other useful commercial products. Active lead compounds can also be further modified to enhance the biological profiles and developed as clinical trial candidates. In this review, the authors will summarize research on many different useful compounds isolated or developed from plants with emphasis placed on those recently discovered by the authors' laboratories as antitumor and anti-HIV clinical trial candidates.