The look for natural drug candidates from marine organisms is that the eternal impetus to pharmaceutical scientists. For the past six decades, marine sponges are a prolific and chemically diverse source of natural compounds with potential therapeutic application. The chemical diversity of natural products is decided by the biological diversity of organisms. The diversity in chemical structures of sponge-derived metabolites is said to an equally diverse pattern of activities starting from anti-fouling to anti-HIV properties. These discoveries have attracted the eye of bioprocess engineers, cell biologists, chemists, geneticist and microbiologists round the world to develop feasible strategies for obtaining sponge-derived metabolites at a bigger scale. Its unique pore structure makes it an excellent host for many marine microorganisms, which account for a large amount of sponge biomass. Some studies have shown that the true source of secondary metabolites in sponges may be their symbiotic microbes.