Biotic stress caused by insects, arachnids, weeds, and especially pathogens including bacteria, fungi, viruses, and nematodes is the major factor threatening the preharvest and postharvest production of vegetable crops. The conventional strategy to control diseases is the application of chemicals, which is harmful to the environment and sustainable agricultural production. Genetic approaches are effective and reliable in maintaining the high productivity of vegetable crops. The resistance genes have been utilized in plant breeding for more than a hundred years. Here I especially focus on the interaction between pathogens and vegetable crops and characterize the major devastating diseases of vegetable crops and the causal pathogens, their pathogenesis, and virulence factors causing diseases. I interpret the two layers of defense responses including cell-surface immunity and intracellular immunity, and the functions of genes involved in immune responses or participating the pathogen infections. I discuss the roles of plant hormones and genes in their signaling pathways in defense responses. I also explore the resistance genes and varieties used in vegetable crop breeding. Studies on the biotic stress and plant defense responses facilitate the application of genetic approaches in vegetable crop breeding.