Hydrogels are hydrated polymers that are able to mimic many of the properties of living tissues. For this reason, they have become a popular choice of biomaterial in many biomedical applications including tissue engineering, drug delivery, and biosensing. The physical and biological requirements placed on hydrogels in these contexts are numerous and require a tunable material, which can be adapted to meet these demands. Tunability is defined as the use of knowledge-based tools to manipulate material properties in the desired direction. Engineering of suitable mechanical properties and integrating bioactivity are two major aspects of modern hydrogel design. Beyond these basic features, hydrogels can be tuned to respond to specific environmental cues and external stimuli, which are provided by surrounding cells or by the end user (patient, clinician, or researcher). This turns tunable hydrogels into stimulus-responsive smart materials, which are able to display adaptable and dynamic properties. In this book chapter, we will first shortly cover the foundation of hydrogel tunability, related to mechanical properties and biological functionality. Then, we will move on to stimulus-responsive hydrogel systems and describe their basic design, as well as give examples of their application in diverse biomedical fields. As both the understanding of underlying biological mechanisms and our engineering capacity mature, even more sophisticated tunable hydrogels addressing specific therapeutic goals will be developed.