Polymer vesicles, also known as polymersomes, are finding increasing applications in biomedical field, including drug delivery, gene therapy, magnetic resonance imaging, theranostics, etc. This is due to their intrinsic hollow nanostructure and compartmentalized domains with diverse functionalities. This review describes recent advances in the design and synthesis of polymer vesicles, including the formation mechanisms, preparation methods, applications and responsive behaviors toward external stimuli. We first present the rational design and synthesis of polymer vesicles based on different polymeric building blocks, followed by an insight into the structure and formation mechanism of polymer vesicles, as well as the recently developed means to determine the exact thickness of the vesicle membrane. Except for responding to traditional stimuli such as pH, temperature and oxidation/reduction, polymer vesicles are becoming ‘smarter’ owing to the newly developed stimuli including electrical field, magnetic field, sugar molecules, gas, ultrasound, etc. Finally, the potential applications of polymer vesicles beyond biomedical field are highlighted as novel nanoreactors, water remediation materials, etc.