Saponins are natural glycosides of steroid or triterpene which exhibited many different biological and pharmacological activities. Notably, saponins can also activate the mammalian immune system, which have led to significant interest in their potential as vaccine adjuvants. The most widely used saponin-based adjuvants are Quil A and its derivatives QS-21, isolated from the bark of Quillaja saponaria Molina, which have been evaluated in numerous clinical trials. Their unique capacity to stimulate both the Th1 immune response and the production of cytotoxic T-lymphocytes (CTLs) against exogenous antigens makes them ideal for use in subunit vaccines and vaccines directed against intracellular pathogens as well as for therapeutic cancer vaccines. However, Quillaja saponins have serious drawbacks such as high toxicity, undesirable haemolytic effect and instability in aqueous phase, which limits their use as adjuvant in vaccination. It has driven much research for saponin-based adjuvant from other kinds of natural products. This review will summarize the current advances concerning adjuvant effects of different kinds of saponins. The structure-activity relationship of saponin adjuvants will also be discussed in the light of recent findings. It is hoped that the information collated here will provide the reader with information regarding the adjuvant potential applications of saponins and stimulate further research into these compounds.