Streptomycetes are the most important bacterial producers of bioactive secondary metabolites such as antibiotics or cytostatics. Due to the emerging resistance of pathogenic bacteria to all commonly used antibiotics, new and modified natural compounds are required for the development of novel drugs. In addition to the classical screening for natural compounds, genome driven approaches like combinatorial biosynthesis are permanently gaining relevance for the generation of new structures. This technology utilizes the combination of genes from different biosynthesis pathways resulting in the production of novel or modified metabolites. The basis for this strategy is the access to a significant number of genes and the knowledge about the activity and specificity of the enzymes encoded by them. A joint initiative was started to exploit the biosynthesis gene clusters from streptomycetes. In this publication, an overview of the strategy for the identification and characterization of numerous biosynthesis gene clusters for polyketides displaying interesting functions and particular structural features is given.