The term polymersome, which refers to a fully synthetic polymeric vesicle, became commonplace around the turn of the millennium. Since then these highly intriguing structures have been at the center of multi-disciplinary research, bridging the fields of nanotechnology, chemistry, physics, biology, medicine and imaging and, more recently, pioneering the field of synthetic biology. As structures they offer greater control into understanding the relationship between amphiphile properties and membrane curvature. Moreover, as delivery vectors for therapeutic and diagnostic compounds they enable greater efficiency of current therapies and targeted delivery. With the rising costs of both healthcare and drug development, polymersomes and nanomedicine are well placed to combat these modern-day problems. This chapter provides an overview of the approaches to prepare and to characterize polymersomes as well as their applications in biomedicine, highlighting recent achievements in the stimuli-responsive drug delivery field.