This chapter reviews the non-replicating antigen delivery systems, including microparticles, liposomes, and immune-stimulating complexes (ISCOMs), which are very useful in vaccine development. The ISCOM matrix is a highly promising structure for use in vaccines, since it complies with all the requirements for a modern adjuvant system. ISCOM based vaccines induce high titers of long-lasting biologically relevant antibodies, which also takes place in the presence of pre-existing specific antibodies. ISCOM-based vaccines induce potent specific cell-mediated immune responses including CD8+ major histocompatibilty complex (MHC) class I restricted cytotoxic T lymphocyte (CTL) responses-which also takes place in the presence of preexisting specific antibodies. Both mucosal and systemic immune responses can be elicited by administering the ISCOM vaccines either by mucosal or parenteral routes. The induced immune responses are protective for long periods of time in many viral, bacterial, and parasitic systems. The ISCOM-based vaccines are likely to combat the infectious diseases for which no adequate vaccines are available. © 2005 Elsevier Inc. All rights reserved.