Since the discovery of penicillin, antibiotics have been instrumental in treating infectious diseases. However, emerging antibiotic multi-resistance coinciding with a nearly exhausted drug pipeline is a major concern for the future of the therapy of infections. A novel approach for the discovery of antibiotics relies on the analysis of microbial consortia in their ecological context, taking into account the potential natural role of antibiotics. Co-cultivations of microorganisms have been successfully applied for the isolation of unknown secondary metabolites including antibiotics, and, thus, open new avenues to the production of bioactive compounds while at the same time providing insight into the natural function of the produced molecules and the regulation of their formation.