The bioavailability of hydrophobic drugs is critically dependent on the development of efficient and safe drug delivery vehicles. Nanoparticulate pharmaceutical carriers commonly used in delivery of active components are often non-ionic in nature. Among them polyether based amphiphiles have become increasingly relevant over the past decades. Polyether based amphiphiles exhibit good chemical stability, high water solubility, low toxicity, have decreased interaction with blood components, and are highly biocompatible; and thus have been applied in biomedical and pharmaceutical areas. The current review highlights the synthetic progression and biomedical applications of these non-ionic polyether-based amphiphilic architectures, some unresolved issues and challenges, along with the future perspective of polyether based nanocarriers for delivery of active components. (C) 2012 Elsevier Ltd. All rights reserved.