Until today, the pathogenesis of rosacea is not known in detail. Yet in recent years evidence has been accumulating that rosacea with its common symptoms such as inflammatory lesions, erythema, telangiectasia, phymatous changes, and ocular symptoms is of inflammatory nature. Tetracycline derivatives like doxycycline successfully used in the treatment of skin diseases like acne and rosacea seem to inhibit different inflammatory pathways involved in the pathogenesis by various modes of action. Although data for skin diseases are relatively scanty, the following modes of action of tetracyclines seem to be most relevant for an effective treatment of acne and rosacea: inhibition of matrix metalloproteinases, downmodulation of cytokines, inhibition of cell movement and proliferation, inhibition of granuloma formation, inhibition of reactive oxygen species, nitric oxide, and angiogenesis, whereas inhibition of phospholipase A2 seems to be of lower importance. The role of the saprophytic mite Demodex folliculorum remains to be clarified. Additional studies are necessary to further elucidate how tetracyclines work in rosacea treatment. Copyright (C) 2009 S. Karger AG, Basel