Detecting pathogens and other causes of human disease can be a challenge for both doctors and the immune system of patients. Recent advancements in optical imaging technology are opening new possibilities for understanding immune system function as well as decentralizing diagnostic imaging. This talk will describe two efforts to watch the battle between pathogens and the immune system, one focused on using high-resolution localization microscopy to understand the molecular mechanisms that control macrophage target recognition and the other based on converting mobile phones into image-based diagnostic platforms. I will introduce a method for profiling cell surfaces with nanometer-scale resolution that is helping to reveal functional differences in the topography of immune cells and their targets, and I will report on the use of mobile phone microscopy to advance diagnosis of parasites in central and west Africa.