Within the setting of hepatic neoplasia [primary and secondary], selective internal radiation therapy [SIRT], also known as radioembolization has become an accepted procedure, incorporated into the armamentarium of multidisciplinary oncologic care. The procedure itself requires an understanding of mesenteric vascular anatomy, tumor vascular patterns, liver metabolism, and chemotherapy. Given the complex nature of the treatment, unique toxicities, and complications may develop from multiple etiologies.Strategies to reduce toxicities and complications as they relate to SIRT can be stratified into two broad categories: factors involving vascularity/vascularization, and factors involving the underlying liver parenchyma. The purpose of this manuscript is to provide the reader with a systematic review of the most commonly presenting toxicities, their etiologies, prevention strategies, and suggested therapeutic options in a practical, and concise manner. A brief discussion on the common misconceptions regarding toxicities will be included.