The sequencing of DNA extracted directly from soil samples suggests that as yet uncultured soil microbes outnumber their cultured counterparts by two to three orders of magnitude.  This uncultured majority no doubt produces secondary metabolites that could serve as molecular probes of biological processes and therapeutic agents.  Uncultivated microorganisms are a very attractive source of potentially new natural products yet they are not amenable to the traditional approaches used to characterize natural products from microbes grown in pure culture.  Although there appears to be no easy way to culture this collection of unstudied microorganisms, it is possible to isolate large fragments of microbial DNA directly from environmental samples and clone this DNA into model bacterial systems in the lab.  We are working on both phenotypic and DNA based strategies for accessing natural products from large environmental DNA libraries.  New tools for identifying environmental DNA derived biosynthetic gene clusters and new natural products produced by these gene clusters will be discussed.