Crop production is challenged by many types of pests induced by different organisms such as fungi, bacteria, insects and viruses. One of the most devastating bacterial plant pathogens is Ralstonia solanacearum. It causes major crop losses in the tropics and subtropics and is a continuing threat in temperate climates. Worldwide, the most important crops affected are potato, tomato and a wide range of ornamentals. Because of its devastating nature and epidemic occurrence, the plant pathogen has a quarantine status in order to prevent outbreaks. R. solanacearum enters the plant root by wounds, from where it moves to the inside of the root and rewrites the plant’s physiology to establish a niche and promote disease. On its way, the bacteria secrete many proteins into the plant cell using a syringe-like mechanism. These proteins are called effectors and often bind to different plant proteins to modify their function, ultimately resulting in a reduction of plant defenses and in an increase in susceptibility. Although these effectors have been extensively studied, almost no plant targets are known. Using different methods, this interaction network between the pathogen and the plant root proteins will be unraveled using tomato as a host. Knowledge about these targets is crucial to understand the disease and to eventually improve crop harvest by increasing resistance against this dangerous pathogen.