Natural products produced by microorganisms have been considered the major resources for drug discovery. However, the production of new and active metabolites becomes difficult and getting gradually higher. Co-culture is one of the best methods for enhancing the production of cryptic metabolites by de silence the biosynthetic pathways. Microbial competition for resources like nutrients and space is proven to be the driving force for the production of bioactive secondary metabolites. It can create a competitive environment for limited space and nutrients may trigger the unexpressed pathways which result in the production of bioactive metabolites due to interspecies interaction. This review focuses on the production of different metabolites from bacteria and fungi by co-culture approach.