The ideal drug-delivery system should provide therapeutics in response to physiological requirements, having the capacity to 'sense' changes and alter the drug-release process accordingly. Such responsive controlled delivery systems are still at an experimental stage. This review focuses on two basic approaches: (1) externally regulated systems (utilizing triggers such as magnetism, ultrasound, temperature and electricity), and (2) self-regulated systems (utilizing pH-sensitive polymers, enzyme-substrate reactions, competitive binding, and antibody interactions).