Nanomedicines in Theranostics are advantageous over standard low-molecular-weight drugs in several different regards. They reduce renal excretion and/or hepatic degradation, leading to prolonged circulation times, reduce the volume of distribution, leading to less accumulation in healthy non-target tissues (‘site-avoidance drug delivery’), improve the ability of drugs to accumulate at pathological sites (‘site-specific drug delivery’) and improve the therapeutic index of drugs, by increasing their accumulation at the target site and/or reducing their localization in potentially endangered healthy organs. In addition, nanomedicine formulations assist low-molecular-weight (chemo-) therapeutic agents in overcoming several additional barriers to efficient drug delivery to pathological sites. We show that theranostic nanomedicines are highly suitable systems for monitoring drug delivery, drug release and drug efficacy. The (pre)clinically most relevant applications of theranostic nanomedicines relate to their use for validating and optimizing the properties of drug delivery systems, and to their ability to be used for pre-screening patients and enabling personalized medicine.