PET/CT guidance during percutaneous tumor ablation procedures combines metabolic and anatomic imaging, providing a powerful approach that can improve intraprocedural tumor visibility and ablation margin evaluation for a variety of cancers. This article reviews key advantages of the use of PET/CT as guidance for tumor ablation and describes the authors' technique for performing such procedures, highlighting the application of PET/CT for each procedural stage, including planning, targeting, monitoring, and assessment of results. Practical considerations in establishing and operating an interventional PET/CT practice are discussed. Suggestions for overcoming logistical challenges that have historically limited procedural PET/CT adoption are proposed. Several emerging procedural approaches relating to PET/CT and other molecular or anatomic imaging technologies are briefly explored.