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Secondary metabolites or natural products have been isolated from many marine organisms. These metabolites often have important bioactive functions; however, very little information is available regarding the biosynthesis and regulation of many secondary metabolites. At a time when use of marine-derived metabolites is rapidly expanding in industry and pharmacological fields, a better understanding of the genetic mechanisms controlling secondary metabolite production is necessary. We review the recent development of a novel transcriptome profiling methodology that allows for rapid and high-throughput screening of changes in mRNA sequence pools. The application of genomics-based techniques and the integration of both biochemical and molecular data sets in marine organisms complement ongoing drug discovery efforts.