Stimuli-responsive polymermaterials are powerful tools in drug delivery and tissue engineering. Because of the large variations in physiological conditions between normal microenvironments and diseased sites, polymer materials with single responsiveness may not achieve the desired goals in a complex physiological microenvironment. Instead, polymer materials responsive to multiple physical or chemical stimuli are highly desired for biomedical applications (e.g., drug delivery). In this review, we highlight recent studies in multi-stimuli-responsive materials with a specific emphasis on polymer particles, films, and hydrogels. The synthetic strategies employed to produce these responsive materials are described. Applications in drug delivery are highlighted, followed by a discussion of the current research focus and future trends.