The first study on application of Design of Experiments (DoE) in optimizing drug formulation appeared in 1967. Since then the number of literature reports on the use of DoE optimization in development of drug delivery technologies has been piling up steadily. Such systematic techniques find their use in every type of conventional dosage form and modern drug delivery system. The drug delivery devices investigated for optimization using response surface methodology include controlled release compressed matrices, microparticulates, macroparticulates, vesicular systems, floating systems, bioadhesive systems, semisolids, transdermals, and inhalations. The optimized processes mainly include extrusion-spheronization, pelletization, microencapsulation, coating, granulation, and tableting. Part I of this article [Crit Rev Ther Drug Carrier Syst 2005; 22(1):27-106] dealt with the salient steps involved in the DoE optimization methodology using diverse experimental designs. Part II deals with various retrospective literature findings as well as the prospective application of such DoE procedures while optimizing varied drug delivery technologies. A vast account of various DoE reports on optimization of diverse drug delivery system and processes along with the critical graphical analysis of various designs, input, and response variables have been presented here in a categorical form. Such an explicit and updated review on drug delivery optimization has not been published anywhere else in the recent past.