Macrophages play a role in almost every disease such as cancer, infections, injuries, metabolic and inflammatory diseases and are becoming an attractive therapeutic target. However, understanding macrophage diversity, tissue distribution and plasticity will help in defining precise targeting strategies and effective therapies. Active targeting of macrophages using nanoparticles for therapeutic purposes is still at its infancy but holds promises since macrophages have shown high specific uptake of nanoparticles. Here, we highlight recent progress in active nanotechnology-based systems gaining pivotal roles to target diverse macrophage subsets in diseased tissues.