Medical devices are becoming key players on health monitoring and treatment. Advances in materials science and electronics have paved the way to the design of advanced wearable, insertable, and implantable medical devices suitable for the prevention and cure of diseases and the physical or functional replacement of damaged tissues or organs. However, intimate and prolonged contact of the medical devices with the human body increases the risks of adverse foreign-body reactions and biofilm formation. Drugs can be included in/on the medical device not only to minimize the risks but also to improve the therapeutic outcomes. Drug-eluting medical devices can deliver the drug in the place where it is needed using lower doses and avoiding systemic effects. Drug-device combination products that release the drug following preestablished rates have already demonstrated their clinical relevance. The aim of this mini-review is to bring attention to medical devices that can actively regulate drug release as a function of tiny changes in their environment, caused by the pathology itself, microorganisms adhesion or some external events. Thus, endowing medical devices with stimuli-responsiveness should allow for precise, on-demand, regulated release of the ancillary drugs to expand the therapeutic performance of the medical device and also should serve as a first step to offer personalized solutions to each patient. Main sections deal with smart drugeluting medical devices that are sensitive to infection-related stimuli, natural healing processes, mechanical forces, electric fields, ultrasound, near-infrared radiation, or chemicals such as vitamin C.