The majority of Gram-negative bacteria are pathogenic to humans and animals. Lipopolysaccharide (LPS) is the most biologically active component of these microorganisms. This compound is also called endotoxin to emphasize its negative impact on a macroorganism. Lipid A, one of the three structural components of the LPS molecule, is responsible for the pathophysiological effects associated with Gram-negative bacteria infections. Although lipid A is considered the conservative component of endotoxin, differences in its structure among species and even strains may occur. These differences concern the type of aminosugars, the degree of substitution of the disaccharide core by fatty acids, phosphate, and/or ethanolamine, and also the type, quantity, and distribution of fatty acids. The lipid A saccharide backbone of the majority of Gram-negative bacteria consists of two glucosamine units in beta (1-->6) glycosidic linkage. Amino groups (at positions 2 and 2') and hydroxy groups (at positions 3 and 3') of glucosamines are commonly substituted by 3-hydroxyfatty acids, most often by 3-hydroxytetradecanoic acid. Other fatty acids (usually saturated, unbranched) are ester-linked to hydroxyacids by their hydroxy group. In lipid A of different microorganisms there is a high diversity of fatty acids, from mirystic (tetradecanoic, 14:0) and lauric (dodecanoic, 12:0) acids and their hydroxylated derivatives to such unique structures as cis-11-octadecenoic acid (Rhodospirillum salinarum 40), 3-hydroxy-5-dodecenoic acid (Phenylobacterium immobile), and iso-2,3-dihydroxytetradecanoic acid (Legionella pneumophila). The saccharide core of some bacterial lipid A may consist of sugars different from glucosamine, e.g., 2,3-diamino-2,3-dideoxy-D-glucose. Other substituents of this part of LPS, besides phosphate groups and ethanolamine, are beta -mannopyranose, 4-aminoarabinose, galacturonic acid, and glycine. Therefore, lipid A, though considered the relatively conservative component of endotoxin, reveals relatively large structural diversity, which influences the variety of LPS biological activity.