Two patients developed kidney failure due to oxalate deposition in the kidney while taking orlistat. Cessation of orlistat was followed by partial recovery of kidney function. The mechanism by which orlistat causes hyperoxaluria and the management of orlistat-induced oxalate nephropathy is reviewed. We suggest that all patients taking orlistat are at risk of this condition, which may develop insidiously and is easily overlooked. Monitoring of kidney function of patients taking orlistat is warranted.