Plants represent an extraordinary reservoir of novel molecules and there is currently a resurgence of interest in the vegetable kingdom as a provider of new lead compounds for introduction into therapeutic screening programs. Plant constituents of interest are usually isolated following a bioactivity-guided fractionation procedure. In order to render this approach more rapid and efficient, the dereplication of crude plant extracts with LC-hyphenated techniques (LC/UV-DAD, LC/MS and LC/NMR) represents a strategic element to avoid finding known constituents and to target the isolation of new bioactive compounds. The development of simple and rapid bioassays; is also crucial for an efficient localisation of active principles. In this respect, the use of bioautographic methods, which enable a direct screening of bioactive constituents on TLC is of great interest. The combination of chemical and biological screening has proved to be very efficient for the survey of an important number of extracts and for the discovery of new lead compounds and several examples of this approach will be discussed in this paper.