Archaeosomes are liposomes made from the polar ether lipids of Archaea. These lipids are unique and distinct in structure from the ester lipids found in Eukarya and Bacteria. The regularly branched and usually fully saturated isopranoid chains of archaeal polar lipids are attached via ether bonds to the sn-2,3 carbons of the glycerol backbone(s). The polar head groups are usually the same as those encountered in the ester lipids from the other two domains, except that phosphatidylcholine is rarely present. These lipid structures provide formulary advantages, and contribute to the excellent physico-chemical stability of the archaeosomes and their efficacy as self-adjuvanting vaccine delivery vesicles. The uptake of archaeosomes by phagocytic cells is several folds greater than that of liposomes made from ester lipids. In addition, archaeosomes enhance the recruitment and activation of professional antigen presenting cells in vivo, and deliver the antigen to both MHC class I and II pathways for antigen presentation, without eliciting overt inflammatory responses. In murine models, systemic administration of archaeosomes containing encapsulated antigen(s) elicits strong and sustained antigen-specific antibody responses which are comparable, in some formulations, to those obtained with Freunds adjuvant. Additionally, archaeosomes promote robust antigen-specific cell-mediated immunity, including CD8+ CTL responses. The immune responses induced by archaeosomes are sustained over long periods and exhibit strong memory responses. More importantly, immunization of mice with archaeosome-based vaccines induces robust protective immunity against intracellular pathogens, and prophylactic and therapeutic efficacies against the development of experimental cancers. Extensive murine model studies suggest that archaeosomes are safe.