Agonists of Toll-like Receptor 2 (TLR2) are attractive synthetic targets due to their use as adjuvants in immunotherapies to treat various diseases notably, cancer. An indepth understanding of TLR2 agonist structure-activity relationships is therefore advantageous for the methodical design of vaccines targetting the TLR2 machinery. This review aims to collate and discuss the literature regarding synthetic studies towards TLR2 agonists and the structure-activity relationships thereof. It is hoped that interested readers will gain a holistic understanding of this topic, and will prompt further efforts towards finding effective agonists of TLR2.