Micro- and macrovascular complications are the main cause of morbidity and mortality in diabetes mellitus. The Na+/H+ exchanger (NHE) is a family of proteins which exchange Na+ for H+ according to their concentration gradients in an electroneutral manner. The exchanger also plays a key role in several other cellular functions including proliferation, differentiation, apoptosis, migration, and cytoskeletal organization. Since not much is known on the relationship between NHE and diabetes mellitus, this review outlines the contribution of NHE to chronic complications of diabetes mellitus, such as diabetic nephropathy; diabetic cardiomyopathy. (C) 2012 Elsevier Inc. All rights reserved.