Bioresponsive hydrogels are emerging with technological significance in targeted drug delivery, biosensors, and regenerative medicine. Their ability to respond to specific biologically derived stimuli creates a design challenge in effectively linking the conferred biospecificity with an engineered response tailored to the needs of a particular application. Moreover, the fundamental phenomena governing the response must support an appropriate dynamic range, limit of detection, and the potential for feedback control. The design of these systems is inherently complicated due to the high interdependency of the governing phenomena that guide sensing, transduction, and actuation of the hydrogel. Future advancements in bioresponsive hydrogels will out of necessity contain control loops similar to synthetic metabolic pathways. The use of these materials will continue to expand as they become coupled and integrated with new technologies.