Natural derived or originated compounds still play a major role as drugs, and as lead structures for the development of synthetic molecules. About 50% of the drugs introduced to the market during the last 20 years are derived directly or indirectly from small biogenic molecules. In the future, natural products will continue to play a major role as active substances, model molecules for the discovery and validation of drug targets. A multidisciplinary approach to drug discovery involving the generation of truly novel molecular diversity from natural product sources, combined with total and combinatorial synthetic methodologies provides the best solution to increase the productivity in drug discovery and development. Screening for new drugs in plants implies the screening of extracts for the presence of novel compounds and an investigation of their biological activities. It is currently estimated that approximately 420 000 plant species exist in nature. For the purpose of lead discovery, or for the scientific validation of a traditional medicinal plant or a phytopharmaceutical, active principals in complex matrices need to be identified. Therefore, the interfacing of biological and chemical assessment becomes the critical issue. Drug discovery from plants can be guided by epidemiologic studies facilitated with computer assisted HPLC microfractionation and microplate technology. Epidemiologic studies have shown that high dietary flavonoid intake may be associated with decreased risk for cardiovascular disease. Chlamydia pneumoniae is a common human pathogen and epidemiological and clinical studies have shown a connection between chronic C. pneumoniae infection, atherosclerosis and the risk of myocardial infarction. We will present here the detection of natural compounds active against C. pneumoniae as an example.