This review focuses on bacteria-fungi interactions mediated by secondary metabolites that occur in the environment and have implications for medicine and biotechnology. Bipartite interactions that affect agriculture as well as relationships involving additional partners (plants and animals) are discussed. The advantages of microbial interplay for food production and the risks regarding food safety are presented. Furthermore, recent developments in decoding the impact of bacteria-fungi interactions on infection processes and their implications for human health are highlighted. In addition, this reviews aims to demonstrate how the understanding of complex microbial interactions found in nature can be exploited for the discovery of new therapeutics.