In the past decades, the vigorous development of nanomedicine has opened up a new world for drug delivery. Hydroxyethyl starch (HES), a clinical plasma volume expander which has been widely used for years, is playing an attracting role as drug carriers. Compared with all other polysaccharides, HES has proven its unique characteristics for drug delivery platforms, including good manufacture practice, biodegradability, biocompatibility, abundant groups for chemical modification, excellent water solubility, and tailorability. In this review, an overview of various types of HES based drug delivery systems is provided, including HES–drug conjugates, HES-based nano-assemblies, HES-based nanocapsules, and HES-based hydrogels. In addition, the current challenges and future opportunities for design and application of HES based drug delivery systems are also discussed. The available studies show that HES based drug delivery systems has significant potential for clinical translation.