Chronic kidney disease is generally thought to be a progressive disorder regardless of etiology. Over the past 15 years, investigations into the mechanisms of disease progression and treatment designed to slow or halt disease progression have been conducted, largely in the adult kidney disease population. Intervention trials have demonstrated that lowering blood pressure in hypertensive patients and administration of drugs that block the renin-angiotensin aldosterone system are effective at slowing kidney disease progression, including diabetes, hypertension, and various glomerular diseases. In addition, novel strategies including anemia therapy with erythropoietin-stimulating agents have been conducted to determine whether treatment of this common complication of kidney disease can stabilize kidney function. Whereas substantial success has been achieved in more common forms of adult kidney disease such as diabetes and hypertension, slowing progression of some immune-mediated glomerular disease such as lupus nephritis and immunoglobulin A (IgA) nephropathy remain a great challenge. Moreover, there is no proven strategy, including multifactorial interventions, that clearly halts progressive chronic kidney disease that has been studied prospectively in a large-scale, long-term trial. The purpose of this review is to discuss these trials, as they form the underpinnings for current clinical practice guidelines in adults with chronic kidney disease.