Mycobacterial glycolipid trehalose-6,6′-dimycolate (TDM) has been extensively studied due to its various biological activities, including toxicity in mice, adjuvant activity, antitumor activity, and anti-infective activity. In addition to natural TDM, various TDM analogues have been synthesized to examine the structure–activity relationship of TDM. The receptor that recognizes TDM remained unknown for many years, until the receptor was identified as macrophage-inducible C-type lectin (Mincle), a C-type lectin receptor expressed on macrophages. Recently, Mincle has been reported to recognize other glycolipids, including cholesterol acyl α-glucoside, a metabolic product of Helicobacter pylori, as well as mycobacterial glycolipids. In addition, Mincle recognizes not only exogenous (glyco)lipids but also various (glyco)lipids released from a damaged cell itself as endogenous ligands, such as β-glucosylceramide, and induces immune responses, such as inflammation.