Bioremediation is an important approach to waste reduction that relies on biological processes to break down a variety of pollutants. This is made possible by the vast metabolic diversity of the microbial world. To explore this diversity for the breakdown of plastic, we screened several dozen endophytic fungi for their ability to degrade the synthetic polymer polyester polyurethane (PUR). Several organisms demonstrated the ability to efficiently degrade PUR in both solid and liquid suspensions. Particularly robust activity was observed among several isolates in the genus Pestalotiopsis, although it was not a universal feature of this genus. Two Pestalotiopsis microspora isolates were uniquely able to grow on PUR as the sole carbon source under both aerobic and anaerobic conditions. Molecular characterization of this activity suggests that a serine hydrolase is responsible for degradation of PUR. The broad distribution of activity observed and the unprecedented case of anaerobic growth using PUR as the sole carbon source suggest that endophytes are a promising source of biodiversity from which to screen for metabolic properties useful for bioremediation.Tremendous increases in the manufacture and consumption of plastics over recent decades have led to numerous ecological and economic concerns. The persistence of synthetic polymers introduced into the environment by human industry poses a major threat to natural ecological systems. The low cost and ease of manufacture have increased global plastic demand more than 150-fold, with the production of 1.5 million tons in 1950 and 245 million tons as of 2006 (21). Despite recognition of the persistent pollution problems posed by plastic, global production is still increasing, with the largest increases expected in developing nations. The sheer volume of plastics produced each year presents a problem for waste disposal systems. The scale of this problem and the recalcitrance of some polymers to degradation necessitate investigation into effective methods for biodegradation of plastics. By gaining an understanding of the mechanisms of polymer degradation, a more efficient technique for the biodegradation of plastic waste can be achieved. To accomplish this goal, researchers need greater knowledge of how compounds are metabolized by existing organisms, an investigation of new organisms with bioremediation potential, and the characterization of novel metabolic capabilities.