Viral diseases of cultivated crops are responsible for the worldwide loss of billions of US dollars in agricultural productivity every year. Historically, this loss has been reduced or minimized principally by the implementation of specific agricultural/phytosanitary measures, and by the introduction of naturally occurring virus-resistance genes into appropriate cultivars by plant breeding. Since the first report of virus-resistant transgenic plants (VRTPs) in 1986, a remarkable diversity of virus-resistance transgenes has been developed. Despite this, to a large part due to controversy surrounding the use of genetically modified organisms, the number of commercially available VRTPs remains small. However, since the potential risks associated with VRTPs were first formulated in the early 1990s, fundamental research on plant–virus interactions and also research specifically aimed at resolving biosafety issues have greatly circumscribed the potential impact of the risks envisaged. Yet, in spite of the advances, both in strategies for creating VRTPs and in the assessment of potential risks, it remains remarkably difficult to weigh the risks/costs and benefits of different means to manage plant viral diseases, and even to make scientifically well-founded choices of the most appropriate strategy for creating VRTPs. Many of the outstanding issues concern the lack of sufficient knowledge of the breadth and durability of the resistance of VRTPs under field conditions. VRTPs will only take their appropriate place in modern agriculture when their potential users will be able to base their choices on realistic assessments of their efficacy, durability, and safety.