An immunomodulator is a substance that stimulates or suppresses the immune system and may help the body fight cancer. The aim of this review is to highlight results of research done on immunomodulators of natural or synthetic origin showing different biological activities. The selection of papers was made using the most relevant scaffolds based on their immunomodulatory biological results. The review also discussed the different synthetic methods for various immunomodulatory drugs such as CC-122. The results showed that many drugs incorporating different scaffolds such as quinazolines revealed promising results for immunomodulatory therapeutic purposes. This work shall hopefully encourage researchers to undertake further work on design and synthesis of new potential immunomodulatory candidates.