During the past 10 years, performing real-time molecular imaging with positron emission tomography (PET) in combination with computed tomography (CT) during interventional procedures has undergone rapid development. Keeping in mind the interest of the nuclear medicine readers, an update is provided of the current workflows using real-time PET/CT in percutaneous biopsies and tumor ablations. The clinical utility of PET/CT guided biopsies in cancer patients with lung, liver, lymphoma, and bone tumors are reviewed. Several technological developments, including the introduction of new PET tracers and robotic arms as well as opportunities provided through acquiring radioactive biopsy specimens are briefly reviewed.