Saponins are biologically active molecules isolated from Quillaja saponaria Molina and Quillaja brasiliensis and are capable of increasing the immunogenicity of antigens in an antigen-adjuvant combination. Saponin adjuvant capabilities were first presented in the 1925 by French veterinarian Gaston Ramon when humoral response was induced while working on diphtheria and tetanus vaccines. Further investigations succeded in reviling the whole palette of chemically different saponins. QS-21 isolated from Quil-A, the primary bark extract of Q.saponaria, is chosen for clinical use based on its physical and chemical uniqueness and belonging therapeutic effects. Despite saponin farmakofor being unknown, there are a few postulated theories that suggest mechanisms of action. Receptor-dependent mechanism proposes saponin interaction with CD2 receptors present on T lymphocytes while receptor-independent, cholesterol-associated internalization still hasn't been rejected. Either way, QS-21 increases the number of antigen-loaded antigen presenting cells (APCs), makes cross-presentation more robust while inducing a mixed Th1/Th2 immune response. Saponins are vaccinologically usable for their antibacterial, antiviral and antitumor properties as well. In attempts for farmakofor reveal, sugar moieties are considered biologically relevant in processes such as receptor stimulation and molecular mimicry of pathogen-associated molecular patterns (PAMPs), C-23 positioned aldehyde group crucial for receptor-associated mechanism and hydrofobic aglicone essential for cholesterol-associated internalization. Structure and activity studies (SAR) are aligned in the opinion that chemical completeness, not the presence or absence of certain functional group, is farmakofor creditable. Also, the synthesis of alternative analogs is needed for the improvement of the toxicity/activity ratio of QS-21, currently the only saponin adjuvant in approved vaccines. With saponin incorporation in immunostimulatory complexes (ISCOM) increasment in stability and decreasment in hemolytic activity is reached. In efficient vaccine design, antigen-adjuvant combination is decisive. Thus, in battle with diseases whose pathogen is intracellular, dominant Th1/Th2 and CTL cytotoxic immune responce is necessary. It is proved that more robust immune response have adjuvant combinations in comparison with adjuvants alone. AS01 and AS15 liposome-based and AS02 emulsion-based formulations are the most intensely studied among all. AS01 is the only one that found its usage in clinical practice because of a suitable risk/benefit ratio for dealing with diseases such as malaria and herpes zoster.