Tomato, one of the most cultivated and economically important vegetable crops throughout the world, is affected by a panoply of different pathogens that reduce yield and affect product quality. The study of tomato–pathogen system arises as an ideal system for better understanding the molecular mechanisms underlying disease resistance, offering an opportunity of improving yield and quality of the products. Among several genes already identified in tomato response to pathogens, we highlight those encoding the transcription factors (TFs). TFs act as transcriptional activators or repressors of gene expression and are involved in large-scale biological phenomena. They are key regulators of central components of plant innate immune system and basal defense in diverse biological processes, including defense responses to pathogens. Here, we present an overview of recent studies of tomato TFs regarding defense responses to biotic stresses. Hence, we focus on different families of TFs, selected for their abundance, importance, and availability of functionally well-characterized members in response to pathogen attack. Tomato TFs’ roles and possibilities related to their use for engineering pathogen resistance in tomato are presented. With this review, we intend to provide new insights into the regulation of tomato defense mechanisms against invading pathogens in view of plant breeding.