Polymer microspheres are considered to be the typical soft materials which are widely used in catalysis, drug delivery, biosensing, microreactors, chemical separation and coating fields because of their unique properties, such as the micro-scale, diffusion, penetration and ease of modification. In order to meet the requirement for use in hostile environments, stimuli-responsive microspheres whose properties significantly change in response to the minor variation of environmental conditions have been developed. This paper reviews the diverse fabrication strategies and morphologies of the responsive polymer microspheres which are sensitive to temperature, pH, magnetic field, ionic strength, light and CO₂ stimulus, respectively. The relevant stimuli-response mechanisms, applications and the demerits of the responsive microspheres are summarized and discussed, then the potential applications and future prospects of the sensitive microspheres are also analyzed.