Interest in the diagnosis and treatment of Fabry disease has been greatly stimulated by the availability of Food and Drug Administration-pproved, effective enzyme replacement therapy. This review will update the progress in this area since enzyme replacement therapy has become available. Fabry disease is often associated with proteinuric chronic kidney disease (CKD), and it appears that the treatment paradigms that have proven to be so effective in diabetes mellitus and other forms of proteinuric kidney disease are also effective in conjunction with enzyme replacement therapy for treating the kidney manifestations of Fabry disease. As such, Fabry disease represents an interesting example of progressive proteinuric kidney disease in which the usual blood pressure is lower than in other forms of CKD. This makes the use of effective antiproteinuric therapy challenging, especially considering the autonomic dysfunction that appears to be part of the disease. Comprehensive therapy for Fabry disease includes enzyme replacement therapy and all of the adjunctive therapies that are currently used to treat all forms of proteinuric CKD. It is anticipated that this approach will preserve kidney function and also benefit the cardiac and cerebrovascular systems in patients with Fabry disease. © 2006 by the National Kidney Foundation, Inc.