In this review paper recent advances in chalcogene mechanochemistry are described. Three selected areas are being covered, i.e. metallurgy, materials science, and medicine. In extractive metallurgy, the processing of copper arsenic mineral enargite (Cu3AsS4) with the aim of its dearsenication and subsequent preparation of a new anticancer drug (Na3AsS4) and of copper in nanocrystalline state (≈ 20 nm) illustrate the non-traditional prospect of ore treatment. In material science, the new nanocrystalline semiconductors were synthesized mechanochemically, e.g. selenides of zinc and lead (ZnSe, PbSe) and bismuth sulphide (Bi2S3). Metal and chalcogene were applied as reaction precursors. In some cases, the amino acids (cystine, cysteine) were applied as sulphur precursor, in order to provide reactive sites on synthesized solid (PbS) for bioconjugation and to prevent agglomeration. The concept of nanomilling is described as a way to prepare eective substances for cancer treatment in medicine. In vitro activity of realgar (As4S4) as an example is described. In all three areas the focus is aimed also on industrial applications where suitable large-scale mills are described. The described examples represent the contemporary aim of mechanochemists to prepare substances with the desired properties in a reproducible way under easyoperating, environmentally friendly and essentially waste-free conditions.