Drought stress poses a significant challenge to plant health and productivity worldwide. On one hand, it can enhance plant defense mechanisms against certain diseases by triggering systemic acquired resistance (SAR) and inducing the production of protective compounds. On the other hand, drought can also compromise the plant’s immune system, making it more vulnerable to infection and disease spread. Therefore, here we explore the physiological and biochemical changes that plants undergo in response to water deficit, discussing the growth patterns, nutrient uptake, and photosynthetic efficiency, followed by exploration of how these drought-induced modifications can influence plant susceptibility to pathogens. We also examine the role of environmental factors and plant genotype in modulating these effects. Practical implications for agriculture and disease management are considered, with a focus on strategies to mitigate the adverse effects of drought on plant disease. In conclusion, understanding the effects of drought stress on plant disease is crucial for developing resilient agricultural systems.