Epidermal growth factor receptor (EGFR) is a receptor tyrosine kinase. Its activation results in beneficial or detrimental consequences, depending on the particular setting. Earlier studies in the animal model of acute kidney injury showed that EGFR activation promotes renal tubular cell proliferation. Activation of EGFR by its exogenous ligands, like EGF, can enhance recovery of renal function and structure following acute kidney injury. However, recent studies indicated that EGFR activation also contributes to development and progression of renal diseases in animal models of obstructive nephropathy, diabetic nephropathy, hypertensive nephropathy, and glomerulonephritis through mechanisms involved in activation of renal interstitial fibroblasts, induction of tubular atrophy, overproduction of inflammatory factors, and/or promotion of glomerular and vascular injury. This review highlights the actions and mechanisms of EGFR in a variety of acute and chronic kidney injuries.