Management of fruit viruses is nearly impossible once plants are infected by the viruses. But there is an decades old technique used for the management of plant viruses known as cross-protection. As the name suggests, mild strains of the virus prevent the infection by the severe strain of the same virus. This technique has been successfully used for the management of many important fruit viruses such as citrus tristeza virus, tobacco mosaic virus, papaya ringspot virus, and apple mosaic virus. The success of the technique depends upon the selection of a suitable mild strain. The mechanism behind cross-protection is explained by the classical view, superinfection exclusion, interference, systemic acquired resistance, and RNA interference. The cross-protection has significance in the management of viruses, along with a few limitations, which can be overcome. Where genetically modified plants come with a baggage of societal, ethical, and environmental issues, cross-protection is the safest technique with minimum ethical clearance requirements. Fruits where this technique has helped in the management of virus infection are apple, citrus, papaya, and tomato.