Derivatives of microbial products targeting Toll-like receptors are currently developed as vaccine adjuvants. The prototypic example is monophosphoryl lipid A, a Toll-like receptor 4 ligand derived from bacterial lipopolysaccharide which is included in approved vaccines to prevent hepatitis B or uterine cervix cancer. There is a growing interest in the development of synthetic Toll-like receptor 4 ligands for novel vaccines aiming at the induction of potent T-cell-mediated immunity. We recently demonstrated that TLR4 is engaged by certain cationic liposomes and we now focus our interest on a distinct family of lipid A mimetics, the aminoalkyl glucosaminide phosphates. Using in vitro models on human myeloid dendritic cells and in vivo models of vaccine responses in mice, we decipher the molecular events involved in the adjuvant activity of these products, paying special attention to their interactions with accessory molecules and to the signaling pathways they preferentially engage. In parallel, we explore the possibility that bacterial glycolipids and analogs which specifically stimulate natural killer T lymphocytes exert adjuvant activity by harnessing interactions with myeloid and plasmacytoid dendritic cells.