 Since the early 1990s, abstract nanoparticle drug delivery systems have been used in the clinic and have evolved to perform additional delivery functions for new therapeutic modalities. Many of these new generation nanoparticles have reached clinical trials and been approved for various indications. A three-year update on the current clinical landscape of nanoparticle drug delivery systems is provided highlighting newly approved nanomedicines, status updates on previous clinical trials, and new technologies that have recently entered the clinic. This article was authored by Aaron C. Enselmo and Samir Mitragotri.