Lichens have attracted considerable interest since ancient time due to their medicinal properties. Lichen produce a variety of orcinol-based compounds such as xanthones, anthraquinones, dibenzofurans, depsides, and depsidones. Several related compounds have shown potent bioactivities as antiviral, antioxidant, anti-herbivore, insecticidal, antifungal, and anticancer. Lichens have been employed as traditional medicines, and these are continuing to be of great interest for their biotechnological potential. The purpose of this review was to systematically evaluate the literature on the orcinol based biologically active secondary metabolites of lichen.