Lipid A, the hydrophobic group of lipopolysaccharide, covers the surface of most Gram-negative bacteria. Lipopolysaccharide, known as endotoxin, can cause fatal disease like sepsis syndrome. Recent studies have shown that it is only the lipid A part of lipopolysaccharide that has the function of endotoxin. After entering the human body, lipid A on the surface of bacteria can stimulate the Toll-like-receptor 4 on the surface of host cells, cause a series of reaction, and produce different cytokines. Here we have discussed the structure, biosynthesis and pathogenesis of lipid A. The application of lipid A in vaccine development was proposed.