Whereas a granulomatous reaction represents a physiologically useful immune defense mechanism against many infections, in autoimmune diseases granuloma formation and the concomitant inflammatory mechanisms may provoke a potentially organ-threatening reaction. Morphologically, several defined sub-types of granuloma have long been known, e.g. foreign body granuloma, tuberculous granuloma,sarcoid, pseudosarcoid, rheumatoid and rheumatic fever granulomas. However, in practice, assigning granulomas to a certain etiology from a biopsy or resection specimen can be a challenging diagnostic process. This article gives a practically oriented overview of the clinically most relevant non-infectious granulomatous diseases. The etiology, epidemiology, clinical correlation and morphology of granulomatous diseases are discussed, focussing on the lungs and skin.