Experience with isolated hepatic perfusion (IHP) is limited to a few centers in the world because of the technical difficulties, surgery-related morbidity, and unproved efficacy in randomized trials. Experimental animal IHP models have led to exploring new ways of improving efficacy, reducing technical difficulties, and minimizing regional and systemic toxicity. Future research should be directed to the identification of suitable biologic or chemotherapeutic agents, defining clinical indications, and development of technical modifications to make it more generally applicable and even repeatable.