Spatial and temporal control of drug delivery is of prime importance for establishing the therapeutic compliance of drugs for various diseases. Conventional approaches to drug delivery for temporal control of drug delivery include encapsulation, entrapment and conjugation to polymeric materials for obtaining the controlled release. Several macro, micro and nanoformulations have been researched and commercialized for producing controlled release of drugs. Apart from the control over the rate of release, a regional delivery would be highly desirable for increasing the efficacy of the drugs and reducing the undue side effects pertaining to the therapy. Some developments in region specific delivery have been utilizing physiological differences of various sites in the body. Topical formulations have been extensively explored for their region specific delivery due to ease of access of these organs like eye, ear, nasal, oral, vaginal and rectal cavities or parts of gastro-intestinal tract like mouth, stomach, intestine and colon. Several sites of the body have not been reached using drug delivery formulations to selectively deliver the drugs to particular organs due to several physiological barriers. Recent developments and approaches in material chemistry, novel polymers, and technology advancements have led to new avenues in the development of nano/micro-carriers or materials for on-demand controlled drug delivery or stimuli responsive drug delivery. On-demand drug release although complex has become possible due to materials which recognize the microenvironments and react in a dynamic way altering properties to cause release of encapsulated drugs within. The current chapter reviews different approaches of developing on-demand drug release using different materials and techniques.