Peptide-based subunit vaccines are of great interest in modern immunotherapy as they are safe, easy to produce and well defined. However, peptide antigens produce a relatively weak immune response, and thus require the use of immunostimulants (adjuvants) for optimal efficacy. Developing a safe and effective adjuvant remains a challenge for peptide-based vaccine design. Recent advances in immunology have allowed researchers to have a better understanding of the immunological implication of related diseases, which facilitates more rational design of adjuvant systems. Understanding the molecular structure of the adjuvants allows the establishment of their structure-activity relationships which is useful for the development of next-generation adjuvants. This review summarizes the current state of adjuvants development in the field of synthetic peptide-based vaccines. The structural, chemical and biological properties of adjuvants associated with their immunomodulatory effects are discussed.