The impact of land use on disease outbreaks is a critical area of study that underscores the intricate relationship between human activities and ecological balance. Intentional modifications of biophysical characteristics, such as deforestation, urbanization, and agricultural conversion, significantly influence disease dynamics. These changes create new habitats for vectors, alter wildlife behavior, and increase the transmission of zoonotic and vector-borne diseases. Historical narratives and modern frameworks like the Land-Use and Land-Cover Change (LUCC) Core Project highlight the urgency of addressing unsustainable practices. Socioeconomic factors and human behavior further complicate these dynamics, making it essential to integrate public health strategies with sustainable land management. This chapter emphasizes the need for interdisciplinary research to develop effective mitigation strategies and policies to reduce the health risks associated with land use changes.