The feasibility of phytoremediation to both remediate and hydraulically contain a methyl tert-butyl ether (MTBE)-contaminated groundwater plume was investigated in a three-phase study that included the following elements: (i) a laboratory bioreactor study that examined the fate and transport of 14C-radiolabeled MTBE in hybrid poplar trees, (ii) a novel approach for a mathematical modeling study that investigated the influence of deep-rooted trees on unsaturated and saturated groundwater flow, and (iii) a field study at a Houston site with MTBE-contaminated groundwater where hybrid poplar trees were planted. In the laboratory study, the predominant fate pathway was uptake and evapotranspiration of [14C]-MTBE from leaves and stems of poplar cuttings rooted in hydroponic solution. The modeling study demonstrates that phytohydraulic containment of MTBE in groundwater by deep-rooted trees can be achieved. The field study demonstrated significant groundwater uptake of groundwater by deep-rooted trees via direct measurement in the first three seasons. The use of vegetation may provide a cost-effective in-situ alternative for containment and remediation of MTBE-contaminated groundwater plumes.