High-protein (HP) weight-loss diets have existed in the United States for decades, although their popularity has recently surged as obesity has become more common. Despite their widespread use, valid concerns exist that HP diets may induce clinically important alterations in renal function and health. HP consumption has been found, under various conditions, to lead to glomerular hyperfiltration and hyperemia; acceleration of chronic kidney disease (CKD); increased proteinuria; diuresis, natriuresis, and kaliuresis with associated blood pressure changes; increased risk for nephrolithiasis; and various metabolic alterations. Unfortunately, a comprehensive understanding of the implications of HP diets is limited by the lack of a universally accepted definition for HP intake, a paucity of rigorous long-term human interventional studies that necessitate relying on short-term or fairly circumstantial evidence, and sparse data on the effects of HP consumption in obese individuals. In addition, matters are further complicated because the renal impact HP diets for limited periods is most likely different than that for more chronic consumption. Nevertheless, although there are no clear renal-related contraindications to HP diets in individuals with healthy kidney function, the theoretical risks should be reviewed carefully with the patient. In contrast, HP diets have the potential for significant harm in individuals with CKD and should be avoided if possible. Because CKD is often a silent disease, all individuals should undergo a screening serum creatinine measurement and urinary dipstick test for proteinuria before the initiation of such a diet.