This review article explores the balance between growth and disease resistance in crops, highlighting recent advances in understanding and managing the trade-offs between these two critical aspects. The authors discuss how plants have evolved a multi-layered immune system to combat pathogens, but this activation often comes at a cost to growth and development. In crops, yield is the primary breeding target, and high disease resistance can significantly impact yield. The review focuses on the role of resistance (R) genes, susceptibility (S) genes, and pleiotropic genes in mediating the growth–defence trade-offs. It provides an update on strategies for optimizing this balance, including fine-tuning NLR genes, modifying S genes, and leveraging pleiotropic developmental genes. The article also explores the potential of natural variation, genome editing, conditional expression, and rational design to breed crops with both high yield and disease resistance. Finally, it discusses the importance of integrating these strategies to achieve sustainable and resilient agricultural systems.This review article explores the balance between growth and disease resistance in crops, highlighting recent advances in understanding and managing the trade-offs between these two critical aspects. The authors discuss how plants have evolved a multi-layered immune system to combat pathogens, but this activation often comes at a cost to growth and development. In crops, yield is the primary breeding target, and high disease resistance can significantly impact yield. The review focuses on the role of resistance (R) genes, susceptibility (S) genes, and pleiotropic genes in mediating the growth–defence trade-offs. It provides an update on strategies for optimizing this balance, including fine-tuning NLR genes, modifying S genes, and leveraging pleiotropic developmental genes. The article also explores the potential of natural variation, genome editing, conditional expression, and rational design to breed crops with both high yield and disease resistance. Finally, it discusses the importance of integrating these strategies to achieve sustainable and resilient agricultural systems.