Stimuli-responsive hydrogels are gaining popularity as ‘smart’ devices in biomedical science, medicine, and tissue engineering due to their exceptional properties such as biocompatibility, high drug loading capability, and on-demand sustained release. These required properties can be achieved by selecting an appropriate polymer, its facile modification, and by tuning the crosslink density in a hydrogel. Stimuli-responsive hydrogels can respond to various physical, chemical, and biological stimuli resulting in structural changes in the hydrogel. These structural changes, such as swelling and shrinkage, provoke the release of a therapeutic drug or biologically active molecule entrapped inside the hydrogel. Multi-responsive hydrogels respond to more than one stimulus and can provide an opportunity to load multiple cargoes for site-specific delivery. However, to realize this concept in practical applications, significant improvement in hydrogel design is still required. Efforts are needed to design an efficient system that can carry multifunctional moieties, can respond quickly to multiple stimuli, and release the payload one by one as required. This chapter highlights the recent progress in the field of stimuli-responsive drug delivery hydrogels, focusing primarily on the design, and working of such vehicles.