Rising from the shortcomings of modern day therapeutics there is a need for a controlled approach in carrier-mediated drug delivery. Polymeric vesicles, also called polymersomes, are powerful tools to address issues of efficacy, specificity, and controlled release of drugs to diseased tissues. These recent, biomimetic structures are able to overcome the body's natural defences, remaining stable for extended time in circulation, have tuneable membrane properties, allowing the control of membrane permeability and therefore of drug release, and have the potential to be functionalized for active targeting of specific tissues, reducing undesirable side effects. Extensive work has been carried out in order to attain multifunctional polymeric vesicles that respond to precise triggers (e.g., temperature, pH, redox, magnetic field, etc) with a spatial and temporal monitoring what may enable unprecedented control of drug release in the body. These versatile structures can be loaded with different type of (bio)molecules and nanoparticles, from drugs to contrast agents for medical imaging, and are able to accommodate them in different subcompartments of the vesicle (i.e., hydrophobic membrane and hydrophilic core). Multimodal targeted delivery system could be obtained from this unique platform, with abilities in both drug delivery and medical imaging contrast enhancement, widening the perspectives toward theranostics. Polymersomes offer a promising route toward more effective treatments with fewer side effects and superior outcomes. WIREs Nanomed Nanobiotechnol 2012, 4:525546. doi: 10.1002/wnan.1183 For further resources related to this article, please visit the WIREs website.