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 temporalcontrol of drug delivery include encapsulation, entrapment and conjugation to polymeric materials for obtaining the controlled release. Several macro, micro and nanoformulations have been researchedand 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 drugsand 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. Topicalformulations 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 ofgastro-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 particularorgans 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 ofnano/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 whichrecognize 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-demanddrug release using different materials and techniques.