The design and development of drug delivery systems involves many different sciences that underpin the research. It is clear that significant advances will only be made through multidisciplinary teams that utilize the latest advances in the biological, chemical, physical, and engineering sciences. The underpinning sciences are also vital to the process of developing successful products. There are three key and interrelated areas of research. (i) Achieve a greater understanding of the biological fate and the targeting of drugs, particularly biopharmaceuticals, macromolecules and macromolecular delivery systems, at the molecular, membrane, and cellular level. (ii) Provide a greater understanding of the physicochemical properties of biopharmaceuticals, macromolecules, and macromolecular delivery systems and how these are modified within a biological environment affecting their activity. (iii) Promote the development of novel materials and delivery systems that will overcome these biological barriers. This article aims to provide a comprehensive review of the key issues to design an effective drug delivery system.