Nanotherapeutics, nanoparticles (NPs) loaded with drugs, show the ability of tissue targeting, long circulation and low toxicity compared with free drugs. Endothelium lying the lumen of a blood vessel is a barrier to restrain tissue deposition of nanotherapeutics. Neutrophils, a type of white blood cells, migrate across endothelium during inflammation. There is an emerging concept that in situ targeting of neutrophils allows delivery of nanotherapeutics into deep tissues at disease sites. Here we summarize the recent advances in delivery of nanotherapeutics to inflammatory tissues or tumor microenvironments via neutrophil infiltration. The studies would shift the current paradigm of nanomedicine to biology-driven design of nanotherapeutics.