In the past decade, polymersomes (also referred to as polymeric vesicles) have attracted rapidly growing interest based on their intriguing aggregation phenomena, cell and virus-mimicking dimensions and functions, as well as tremendous potential applications in medicine, pharmacy, and biotechnology. Unlike liposomes self-assembled from low molecular weight lipids, polymersomes are in general prepared from macromolecular amphiphiles of various architectures including amphiphilic diblock, triblock, graft and dendritic copolymers. Polymersomes exhibit very unique features highlighted with high stability, tunable membrane properties, versatility, and capacity of transporting hydrophilic as well as hydrophobic species such as anticancer drugs, genes, proteins, and diagnostic probes. Recently, much effort has been directed to the development of intelligent polymersomes that respond to internal or external stimuli, in particular, pH, temperature, redox potential, light, magnetic field, and ultrasound, either reversibly or nonreversibly. Stimuli-sensitive polymersomes have emerged as novel programmable delivery systems in which the release of the encapsulated contents can be readily modulated by the stimulus. The stimuli-responsive release may result in significantly enhanced therapeutic efficacy and minimized possible side effects. It is also feasible to form and disassemble polymersomes in water simply by applying an appropriate stimulus. In this article, recent advances in stimuli-sensitive polymersomes have been reviewed, and perspectives on future developments have been discussed.