The search for microorganisms from novel sources and in particular microbial symbioses represents a promising approach in biotechnology. In this context, lichens have increasingly become a subject of research in microbial biotechnology, particularly after the recognition that a diverse community of bacteria other than cyanobacteria is an additional partner to the traditionally recognized algae-fungus mutualism. Here, we review recent studies using culture-dependent as well as culture-independent approaches showing that lichens can harbor diverse bacterial families known for the production of compounds of biotechnological interest and that several microorganisms isolated from lichens, in particular Actinobacteria and Cyanobacteria, can produce a number of bioactive compounds, many of them with biotechnological potential.