Cauliflower is a globally significant vegetable crop, valued for its edible curd. However, its cultivation faces substantial challenges due to biotic stresses, including fungal, bacterial, and viral pathogens and insect pests, which lead to severe yield and quality losses. Traditional control measures, such as chemical pesticides, are often ineffective in the long term and raise environmental and economic concerns, necessitating sustainable approaches to enhance resistance. Biotic stress resistance in cauliflower is a complex trait governed by qualitative and quantitative genetic factors. Breeding programs focus on incorporating resistance genes from wild relatives or related species into elite varieties. Advanced molecular tools, such as marker-assisted selection (MAS), genomic editing (e.g., CRISPR/Cas9), and transcriptomic studies, are accelerating the development of resistant cultivars. These tools enable precise identification and manipulation of resistance genes and regulatory networks involved in defense mechanisms, such as pathogen recognition, signal transduction, and production of antimicrobial compounds. Integrated strategies combining resistant varieties, cultural practices, and integrated pest management (IPM) are critical for sustainable cultivation. This book chapter highlights recent advances in biotic stress resistance in cauliflower, emphasizing challenges, molecular mechanisms, and innovative breeding strategies. Sustainable biotic stress management will ensure improved productivity and reduced reliance on chemical inputs, supporting environmentally friendly agriculture.