Yttrium-90 microspheres are increasingly being used as a treatment modality for primary and secondary liver tumors. As these therapies continue to be accepted, it is natural that their application in more complex clinical scenarios will become more common. This article is meant to introduce these controversies and to generate interest and dialogue by the interventional oncology community. This discussion is based on more than 900 (90)Y radioembolization procedures performed over a 5-year period.