Wheat is grown on about 10 million ha in the tropical highlands and lowlands of the world, where it is an important food source. Many farmers in these areas work under subsistence conditions. Wheat diseases in tropical regions can be severe and require significant efforts to control. For economic and environmental reasons, host plant resistance is the most appropriate and sustainable disease control method. We describe highland and lowland tropical wheat regions and discuss CIMMYT's breeding strategies, philosophies, and progress in developing resistance to the major diseases such as rusts, foliar blights, fusarium scab, BYD, and spot blotch. Additionally, we review the role of national wheat research programs and beneficial spillovers of our combined breeding efforts to other wheat production areas of the world.