The rapid advancement of biomedical research has led to many creative applications for biocompatible polymers. As modern medicine discerns more mechanisms, both of physiology and of pathophysiology, the approach to healing is to mimic, or if possible, to recreate the physiology of healthy functioning. Thus, the area of smart polymers for responsive drug delivery has evolved. The developments fall under two categories: externally regulated or pulsatile systems (also known as 'open-loop' systems) and self-regulated systems (also known as 'closed-loop'). The externally controlled devices apply external triggers for pulsatile delivery such as: ultrasonic, magnetic, electric, light and chemical or biochemical agents. The self-regulated systems, on the other hand, are defined as systems where the controlled variable is detected, and as a result, the system output is adjusted accordingly. The release rate is controlled by feedback information, without any external intervention. The self-regulated systems utilize several approaches for the rate control mechanisms such as thermal, pH-sensitive polymers, enzyme-substrate reactions, pH-sensitive drug solubility, competitive binding, antibody interactions and metal-concentration-dependent hydrolysis.