Potato is a major food crop that has the potential to feed the increasing global population. Potato is the fourth most important crop and a staple food for many people worldwide. The traditional breeding of potato poses many challenges because of its autotetraploid nature and its tendency toward inbreeding depression. Moreover, potato crops suffer considerable production losses because of infections caused by plant viruses. In this context, RNA silencing technology has been successfully applied in model and crop species. In this review, we describe the RNA interference (RNAi) mechanisms, including small-interfering RNA, microRNA, and artificial microRNA, which may be used to engineer resistance against potato viruses. We also explore the latest advances in the development of antiviral strategies to enhance resistance against potato virus X, potato virus Y, potato virus A, potato leafroll virus, and potato spindle tuber viroid. Furthermore, the challenges in RNAi that need to be overcome are described in this review. Altogether, this report would be insightful for the researchers attempting to understand the RNAi-mediated resistance against viruses in potato.