Numerous local treatment strategies now exist for patients with primary and metastatic liver tumors. Increasingly, patients who cannot be adequately treated with a single form of focal therapy, go on to receive a variety of sequential treatments. However, the impact of each prior therapy on subsequent treatments and the cumulative toxicity of these therapies remains uncertain. Yttrium-90 radioembolization is becoming an increasingly common treatment for patients with hepatic malignancies. Though the baseline toxicity of radioembolization is low, greater care must be taken when treating patients who have undergone prior hepatic treatments. While this population can be treated safely, additional measures should be taken to ensure that patients are carefully screened and all effort is made to minimize liver toxicity.