The accumulation of unfolded proteins in the endoplasmic reticulum (ER), leading to ER stress, is caused by a wide range of physiologic and pathologic conditions. Cells respond to ER stress by activating a series of integrative stress pathways termed the unfolded protein response (UPR). This either may be adaptive and promote cell survival, or if the ER stress is chronic or excessive, may lead to cell death. The role of ER stress in the pathophysiology of both acute and chronic kidney diseases has been gaining increasing interest. This review highlights the current knowledge of ER stress in renal disease, with emphasis on more recent advances. Potential therapeutic options targeting ER stress are discussed.