Plum pox virus (PPV), a Potyvirus, is the causal agent of sharka, the most detrimental viral disease affecting stone fruit trees. This review focuses on research carried out to obtain PPV- resistant transgenic plants and on how biotechnological strategies evolved in light of the scientific advances made during the last several years. Successful RNA silencing strategies that confer high level of resistance to strains of PPV have been developed and tested under laboratory and greenhouse conditions. Moreover, field tests showed that transgene-mediated RNA silencing was effective in protecting plum plants against aphid-mediated PPV infection. The new emerging biotechnological approaches for conferring PPV resistance are discussed.