Balkan endemic nephropathy is a unique renal fibrosis leading to progressive and gradually developing renal failure, followed by development of tumors of the urinary tract. Several hypotheses concerning the etiology of this disease have been investigated, including environmental factors (heavy metals, polycyclic aromatic hydrocarbons, aromatic amines, fungal and plant toxins) and/or genetic factors. The article reviews the different hypotheses and pays particular attention to the biochemical role of the mycotoxin ochratoxin A and the plant product aristolochic acid.