With the increasing popularity of E-cigarettes, chronic exposure to nicotine (NIC) is emerging as a novel risk factor for the kidney. NIC increases oxidative stress in the kidneys, which impairs the viability and function of renal tubular and endothelial cells, alters renal hemodynamics, and compromises overall kidney function. Moreover, long-term NIC exposure increases the risk of development and progression of chronic kidney diseases and may escalate the impact of coexisting morbidities such as obesity-associated renal disease, hypertension, renal transplant status, or the toxicity of various anticancer agents. In this review, we summarize experimental findings describing increased renal risk of chronic NIC exposure and explore therapeutic interventions to alleviate adverse effects of NIC. .