Since the introduction of the liposomal doxorubicin formulation Doxil/Caelyx on the market 20 years ago, a number of targeted nanomedicine formulations have become part of treatment regimens in the clinic. An update will be given of problems encountered and current strategies to tackle them. The preclinical use of nanomedicine formulations for therapeutic and diagnostic applications is increasing exponentially. Many different systems and strategies have been developed for drug targeting to pathological sites, as well as for visualizing and quantifying important (patho-) physiological processes. In addition, ever more efforts have been undertaken to combine diagnostic and therapeutic properties within a single nanomedicine formulation. These so-called nanotheranostics are aimed to provide valuable information on drug delivery, drug release and drug efficacy, and they are considered to be highly useful for personalizing nanomedicine-based (chemo-) therapeutic interventions.