Natural products produced by biological organisms have played an important role in human health. The genomes of several Aspergillus species and several Streptomyces species have recently been sequenced. Interestingly the genomes revealed a large range of secondary metabolite genes, for many of which the products are currently unknown, suggesting that there is a wealth of secondary metabolites yet to be discovered. This brief review will discuss the current knowledge in polyketides produced by the various different classes of polyketide synthases (PKSs) present in the Aspergillus and Streptomyces genomes.