A way to overcome a drug’s side effects is by its more efficient delivery to diseased sites. This can be accomplished by nanoparticles, tiny carrier vehicles that can be loaded with drugs, known as nano medicines (1,2). The most matured and widely applied nanoparticle delivery systems are polyethylene glycol (PEG) coated liposomes (3). These bilayered vesicles of phospholipids used for drug delivery typically measure ~100 nm in diameter. Doxil, a liposomal formulation of doxorubicin, was the first nanoparticle drug formulation to be approved for clinical use. Since Doxil’s introduction in 1995, the nanomedicine field has undergone exceptional growth, which is exemplified by the increasing number of papers published and by the implementation of large federal programs that fund nanomedicine research. Whereas Doxil represents a first generation nanomedicine, the current focus is on controlled releases systems whose sizes and compositions can be judiciously fine-tuned. Such self-assembled nanoparticles are widely used as delivery vehicles for poorly water-soluble compounds, and some of these have entered clinical trials. The majority of these self-assembled structures have problems with drug loading stability, which is strongly influenced by the in vivo environment. Interactions between polymeric nanoparticles and blood components have been reported to cause drug leakage. Therefore, thoroughly understanding in vivo drug-carrier association stability and dissociation kinetics should improve delivery efficiency and, as a result, therapeutic efficacy. Imaging techniques, including MRI, can monitor the drug-carrier association and help identify key parameters that determine drug-carrier compatibility. These findings can serve as drug delivery efficiency guidelines that can be applied to improve nanomedicines. Despite nanomedicine’s promise and the field’s research activity, its potential is not being fully met and implementation in clinical care is falling behind. In part this is due to the technology’s immaturity, but – more importantly – ways to stratify patients that may benefit from nanomedicine-based therapy are nonexistent. The ability to non-invasively evaluate nanomedicine targeting would greatly improve patient care by allowing swift adjustments in dosage and/or treatment regimen. Strategies in which nanoparticle drug formulations are labeled for imaging-facilitated delivery are extensively studied (4,5). Unfortunately, such theranostic approaches have little clinical relevance. As has been shown for antibody therapy, an easy-to-prepare companion diagnostic for quantitative imaging of nanomedicines can overcome these issues. Practically, the companion diagnostic could be applied to screen for patient amenability, but could also be used as an agent that is co-injected with the actual nanotherapy to aid in treatment continuation decision. In this educational imaging-facilitated optimization of nanomedicine and the “companion diagnostic" concept, the latest advances in these fields, and translational considerations will be discussed.