Plant virus diseases cost producers billions of dollars each year by reducing crop yields and quality. Although producers minimize the impact of many virus diseases through a variety of management practices, introduction of new viruses and mutation of existing ones has continually challenged those involved in virus disease control. Biological control is a term not generally associated with control of plant virus diseases. The chapter reviews the potential of using cross protection as a biological control for plant virus diseases. Cross protection has been known by many names: acquired immunity, acquired tolerance, cross immunization, and premunity. Because morphological changes in a virus-infected plant would probably not account for specificity in cross protection, the area that has received the most interest is that of physiological changes in the protected plant. The initial virus infection establishes a mechanism for virus spread throughout the plant.