Abstract: In the past decades,only 1% of the microorganisms were cultured and isolated repeatedly,thus it became more difficult for the potential of yielding metabolites with diverse structures and promising biological properties.Uncultured microorganisms (99%) were usually defined as “microorganisms that could not grow in pure culture on synthetic media in vitro”.Recently,in order to solve this problem,numerous in situ cultivation-based methods for culturing microorganisms have been developed.These methods could provide the simulated natural environment sand the intercellular communications in multispecies microbial communities,so they could improve the probability of microbial cultures.On the basis of in situ  cultivation methods,some new cultivable techniques were developed,including diffusion chamber and isolation chip,etc.This review described the isolated and in situ cultivation-based methods of uncultured microorganisms and the importance of a new source of lead compounds in drug discovery.

Key words: uncultured microorganisms, in situ cultivation, natural products, culture methods