Atherosclerotic renal artery stenosis (ARAS) is a common and complicated disease, which can result in high blood pressure and loss of kidney function. Although progress has been made in the understanding and treatment of hypertension in relation to ARAS, much less progress has been made in the area of renal function. Here we discuss current treatment options in regard to medical therapy and revascularization. We also describe the proposed mechanisms leading to renal dysfunction, including the CD40 signaling cascade, which is a particularly attractive signaling mechanism that may provide a mechanistic rationale for the development of renal disease in ARAS.