Heat from radionuclide decay causes coupled thermal (T), hydrological (H), chemical (C), and mechanical (M) processes in the rock mass. These coupled processes impact the ability of a repository to isolate waste by affecting water seepage into waste-emplacement drifts and by affecting radionuclide transport. The U.S. Department of Energy's Thermal Testing Program at the proposed high-level radioactive waste repository at Yucca Mountain, Nevada, began in the mid-1990s and consisted of three large-scale in situ thermal tests. Although in 2010, the U.S. government decided to pursue alternative solutions to geologic disposal of radioactive waste at Yucca Mountain, the work reported throughout this volume refers to “the proposed repository” at Yucca Mountain, which was the status at the time the chapters were written (2009). The main objective of these thermal tests was to gain an in-depth understanding of the coupled THCM processes that would occur in the repository rock. Numerical models that capture coupled processes were constructed for the respective thermal tests, and the predictions from these numerical models, when compared to measured data, enabled the evaluation of processes occurring in the thermal tests. In turn, analysis of the thermal tests, particularly of the drift-scale test (the largest of these tests), has provided information on THCM processes that were incorporated in drift-scale and mountain-scale numerical models for the proposed repository at Yucca Mountain to predict repository performance during thermal loading. Such coupled-processes models for the proposed repository show that TH processes would produce a vaporization barrier, which would prevent water from seeping into the drifts when the temperature near the drifts rises above boiling. THC and THM processes cause permeability changes that modify flow paths near the drifts and, in turn, seepage of water into drifts. The impact of thermally driven coupled processes is largest near the drifts, where the increase in temperature is the greatest. Further away (tens of meters) from the drifts, the impact of THCM processes on radionuclide transport is insignificant. The detailed THCM studies at Yucca Mountain indicate that, overall, the effects of heating due to radioactive decay would not degrade the long-term ability of the proposed repository to isolate waste. On the contrary, the THCM coupled processes lead to more diversion of water around and less seepage into the waste-emplacement drifts than that at ambient conditions, thus making Yucca Mountain a more effective natural barrier to potential release of radionuclides to the biosphere.