Plant viruses, being obligately intracellular parasites, cause widespread infections in plants. They are dependent on the biochemical mechanisms of the host plants for their replication and dissemination, causing several symptoms and resulting in huge economic losses. Viral diseases in vegetable crops seriously impact the growth and yield of these crops, thereby threatening food security. Pathogenesis, the process by which these viruses cause diseases in crops, is associated with a complex interplay between the respective virus and the host. This entails virus entry into the plant cell, replication, intercellular movement, systemic spread, and the resultant host responses that in turn manifest as specific disease symptoms. The defense mechanisms of the plants and the strategies devised by the viruses to evade the plant defenses are critical aspects of this process. Given the enormous diversity of these viruses, the variety of vegetable crops that are affected, and the insect vectors involved in the transmission of plant viruses, there is a compelling need to examine the molecular biology and pathogenesis of these viruses in order to devise integrated management approaches against viral infection and spread. This chapter presents the recent advancements made over the past 5–10 years regarding mechanisms of infection biology and pathogenesis of major plant viruses infecting vegetable crops, as well as their complex interactions with their hosts. Our chapter will serve as an insightful theoretical source for the latest information on viral infection and pathogenesis mechanisms in vegetable crops.