In situ chemical oxidation (ISCO) is one approach for remediation that involves delivery of chemical oxidants into the subsurface to achieve organic contaminant mass reduction in source areas as well as control and treatment of groundwater plumes. The oxidants most commonly employed include peroxide, permanganate and ozone systems, with delivery into the subsurface accomplished using wells, probes, fracturing, and mixing systems. The choice of oxidant and delivery method is site-specific and dependent on contaminant type and concentration and the subsurface hydrology and geochemistry of the formation. Field-scale applications of ISCO have now occurred at more than 100 sites in the U.S., while the technology is still evolving and the standard of practice is being established. Application to sites contaminated by dense nonaqueous phase liquids (DNAPLs) remains especially challenging and the process principles and effective practices for application of ISCO at DNAPL sites are still evolving. There is a theoretical basis for degradation of DNAPLs by ISCO. Chemical oxidants in the aqueous phase in contact with a DNAPL in the subsurface can enhance the interphase mass transfer rate from the nonaqueous to aqueous phase wherein the DNAPL organics are oxidatively destroyed through chemical reactions involving redox or free-radical processes. This degradation process requires that the oxidant be transported through the porous media to the DNAPL surface and that the DNAPL compounds are susceptible to oxidation by the oxidant being applied. Moreover, it requires that oxidant interaction with the subsurface does not produce heterogeneities or other transport effects that prevent oxidant-DNAPL interaction, and that the interphase mass transfer resistance does not increase due to film formation or other interfacial effects. During this presentation, highlights of relevant theory, experimental results, and field observations will be given concerning the application of ISCO for source control and remediation at DNAPL contaminated sites.