The growing use of group AB plasma in the United States in recent years poses unique challenges to blood centers and transfusion services. Blood centers must collect sufficient plasma components from a limited pool of group AB donors while taking steps to improve transfusion safety that further restricts the available supply. Transfusion services, on the other hand, must use the finite resource in the most conscientious and medically appropriate manner. Recently, many investigations have challenged long-held beliefs about transfusion practice and appropriate indications for blood components across a variety of specialties. Balancing supply and demand of group AB plasma requires collaboration between blood suppliers and transfusion services, and opportunities for improvement exist on both sides of the equation.