Anthropogenic compounds used as pesticides, solvents, and explosives often persist in the environment and can cause toxicity to humans and wildlife. The persistence of anthropogenic compounds is due to their recent introduction into the environment; microbes in soil and water have had relatively little time to evolve efficient mechanisms for degradation of these novel compounds. Some anthropogenic compounds are easily degraded, while others are degraded very slowly or only partially, leading to accumulation of toxic products. This review examines the factors that affect the ability of microbes to degrade anthropogenic compounds and the mechanisms by which novel pathways emerge in nature. New approaches for engineering microbes with enhanced degradative abilities include assembly of pathways using enzymes from multiple organisms, directed evolution of inefficient enzymes, and genome shuffling to improve microbial fitness under the challenging conditions posed by contaminated environments.Anthropogenic chemicals are widely used in agriculture, industry, medicine, and military operations. Examples include pesticides such as atrazine, pentachorophenol (PCP), 1,3-dichloropropene, and DDT, explosives such as trinitrotoluene (TNT), solvents such as trichloroethylene, and dielectric fluids such as PCBs. There was little concern over the fate of anthropogenic chemicals in the environment until the late 20 th century. Adverse effects on wildlife eventually focused attention on the fact that some anthropogenic chemicals persist in the environment because they are not readily degraded by microbes. However, some anthropogenic compounds, such as atrazine, are degraded remarkably quickly. Others, such as paraoxon, are efficiently detoxified, although not degraded. This review will examine how microbes assemble novel pathways for detoxification or degradation of anthropogenic compounds and how the efficiency of biodegradation can be enhanced by optimizing naturally occurring pathways and by patching together novel pathways using enzymes from different organisms.Microbial enzymes that act upon anthropogenic compounds arise from promiscuous activities of previously existing enzymes. Promiscuous enzymes can evolve to become more effective catalysts as a result of selective pressure for detoxification of a toxic compound or use of a novel source of carbon, nitrogen, or phosphorus. Detoxification often requires only a single step. For example, PCP is toxic because it dissipates trans-membrane proton gradients, and thereby uncouples oxidative phosphorylation 1,2 . Phanerochaete chrysosporium detoxifies PCP by methylating the hydroxyl group, thus eliminating its ability to transport protons across a lipid bilayer 3 . Figure 1. Atrazine is the most widely used pesticide in the world. Three steps that replace the substituents on the ring with hydroxyl groups convert atrazine into cyanuric acid, which is readily metabolized, either within the same microbe (e.g. Pseudomonas sp. strain ADP), or by other microbes. 4 PCP is used pri...