Nanomedicine systems aim to improve the biodistribution and the target site accumulation of systemically applied (chemo-) therapeutics. By increasing drug localization at the pathological site, and by reducing its accumulation in healthy organs and tissues, the efficacy of the intervention can often be increased, while its toxicity can be attenuated. Using HPMA copolymers as a model macromolecular nanomedicine system, and several selected examples of recently published proof-of-principle reports, we here show that besides for standard drug delivery purposes, polymeric nanomedicines can also be employed for image-guided drug delivery, as well as for tumor-targeted combination therapy. (C) 2010 Elsevier Ltd. All rights reserved.