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Guayule (Parthenium argentatum Gray) is an arid-adapted, low-input perennial shrub native to Mexico and southern Texas that has received considerable attention as an alternative source of natural rubber. It has potential to replace the most common types of rubbers, including synthetic rubber derived from petroleum and natural rubber, which is tapped from Hevea (Hevea brasiliensis) trees grown in tropical regions, primarily Southeast Asia. The guayule plant produces natural rubber in its bark parenchyma cells and the shrub is processed to extract the latex. Guayule rubber is comparable in quality to Hevea natural rubber and the residual, non-latex guayule plant material can be transformed into valuable co-products, such as bioenergy. This review introduces the reader to guayule rubber production (agriculture, processing and products) and explores the sustainability implications of guayule rubber commercialization related to the three pillars of sustainability, including environmental impacts of rubber production, economic barriers and advantages, and social implications. The review highlights areas of focus that could be leveraged to help guayule become a more sustainable source of natural rubber. Guayule rubber provides an opportunity to lower the environmental impacts of a major commodity, to develop an industry to support the local U.S, economy, and to reduce U.S. dependence on non-renewable petroleum sources and rubber imports. Proposed recommendations to further support guayule sustainability include improving the efficiency of agricultural and processing activities, utilization of guayule co-products to improve economics of guayule cultivation, and the establishment of a secure guayule rubber supply at a production level that could consistently meet rubber demands. A better understanding of guayule rubber life-cycle impacts could be a way to reduce the environmental footprint of guayule rubber products and expedite its commercialization. (C) 2015 Elsevier B.V. All rights reserved.