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. The molecular underpinnings of these botanicals, including the activities of nitric oxide, adhesion molecules and cytokines are reviewed. Two case studies will highlight the therapeutic effects of the immunomodulators. In addition, the pros and cons of utilizing the current research to inform the clinical use of the immunomodulators will also be discussed.