This chapter discusses the principal effects of lichen growth on mineral substrata and focuses on rock surface disintegration, on mineral etching patterns and decomposition features, and on the formation of biogenic minerals. The chapter discusses the principal effects of lichen growth on mineral substrata with reference to rock surface disintegration, mineral etching patterns, and formation of oxalates, iron oxides, and hydroxides, aluminosilicates, and lichen acid–metal complexes. The release of organic molecules, such as oxalic acid and polyphenolic secondary products of lichen metabolism usually indicated as “lichen acids,” have been proven to play a key role in lichen weathering and neogenesis of poorly and well crystalline biominerals. Both physical and chemical properties of the rock substrate and morphology of the thallus may strongly differentiate extent and assemblage of the lichen–substrate contact zone. Differences in the bio-weathering capability seem to be more related to the physiology of the lichen species involved. Recent progress in the study of the interactions between lichens and their rock substrata mainly relies on the utilization of specialized analytical and instrumental techniques and on the close collaboration among scientists from different research fields.