The liver is frequently affected by metastases from different tumor entities. In most cases, Surgical resection provides the greatest potential for cure in secondary liver tumors; however, surgery can be offered only to a limited part of patients (~20%). In selected patients, image-guided minimally invasive treatment such as percutaneous RF ablation takes the role as a palliative treatment option with curative intention especially in patients who are technically and/or medically not eligible for surgery. According to the BCLC guidelines, RF ablation has a clear indication in patients suffering from early-stage HCC with one to three nodules of up to 3 cm who are not eligible for surgery. In selected patients with very early HCC, it seems that RF ablation might be the treatment of choice even in patients who are fit for surgery. RF ablation is accompanied by an acceptable mortality and morbidity. Although usually “unfavorable” patients in a highly palliative situation are treated with RF ablation, local tumor control by RF ablation is often as good as or even better than systemic chemotherapy. Combination of RF ablation with other treatments is an area of ongoing active research. It is highly desirable to implement local ablative therapies such as RF ablation in the treatment algorithm for non-resectable liver tumors not only as third-line or salvage but also as second- or first-line treatment in early HCC probably, in metastatic disease, in combination with systemic therapy. RF ablation should always be embedded in a multidisciplinary treatment strategy tailored to the individual patient and to the features of the disease (“customized therapy”). Patient selection is very crucial for successful treatment with RF ablation. It should be based upon tumor site and size, proximity of large vessels, bleeding risk, respiratory motion, probe pathway, and last but not least the physician’s experience. The technique is operator-dependent with a steep learning curve. Until the role of RF ablation within a multimodal treatment strategy for liver tumors is completely defined, RF ablation should be restricted to centers with highly experienced interventionalists incorporated into an interdisciplinary oncology team.