The last few decades have provided increasing evidence that immunomodulators are efficacious in a variety of diseases. However, the molecular modes of activity are rarely mentioned. In this lecture, the molecular underpinnings, including the activities of nitric oxide, adhesion molecules and cytokines will be discussed. Research on the immunomodulators will also be discussed as well as the pros and cons of utilizing the current research to inform the clinical use of the immunomodulators.