The rise in antimicrobial resistance is a global concern which must be urgently tackled by the introduction of novel antibiotics to the drug development pipeline. The immense chemical diversity observed in natural environments includes secondary metabolites produced by microorganisms with potential antibiotic properties. The challenge is to develop methods to access the often hidden capacities of microbial communities. Studying the interactions of microorganisms is a developing, yet powerful methodology to identify novel bioactive compounds. In this chapter we review microbial co-cultivation in the context of drug discovery, with special emphasis on bacteria and fungi, as well as discuss the current challenges and perspectives of the field.