Marine sponges are an ancient and diverse animal phylum that host well-established symbiotic microbial communities. The vast majority of the microbial genetic diversity in sponges is, however, currently inaccessible by traditional methods. This large genetic resource may be of use for biotechnological applications, particularly as the physicochemical parameters under which the genes within these microbes function are likely to dictate that they may be significantly different from similar genes or gene products currently in use in industry, offering in some instances improved performance. Emerging tools and technologies in the field of metagenomics offer enormous potential for the discovery and exploitation of new biosynthetic entities. Both sequence-based and function-based technologies have to date been employed to identify genes with novel or improved functions. Marine sponges, as well-recognized sources of novel marine natural products with varied applications, are the ideal target for the implementation of these new technologies. We detail here some successes in the discovery and development of marine natural products for industrial or pharmaceutical applications and we also highlight some technical impediments to gene and gene product exploitation which as yet still need to be overcome.