Currently, three types of primary hyperoxaluria (PH I – III) are known, all based on different gene-mutations affecting the glyoxylate metabolism in the liver. Disease hallmark is an increased endogenous oxalate production and thus massively elevated urinary excretion of oxalate and other type-specific metabolites. Hyperoxaluria induces the formation of calcium-oxalate kidney stones and/or nephrocalcinosis. In addition to that, a chronic inflammatory activation by hyperoxaluria per se, often leads to an early deterioration of kidney function, regularly resulting in end-stage renal disease (ESRD) at least in patients with type I PH. Except for vitamin B6 treatment in PH I, therapeutic regimen consisted only of supportive measures, like significantly increased fluid intake and medication increasing the urinary solubility like alkaline citrate. Now, a new treatment option, RNAi, is available, currently only for type I PH.