ISCOMATRIX adjuvant is capable of inducing broad and potent humoral and cellular immune responses. The components are well defined and the manufacturing process is simple and robust. Many vaccines containing the ISCOMATRIX adjuvant have been tested in a range of animal models, including human and non-human primates. Strong antibody and T cell responses have been induced in these studies. The antibody response is often achieved with lesser amounts of antigen than other adjuvant systems and the maximal responses have also been reached more quickly. Both CD4+ and CD8+ T cell responses are induced with the cytotoxic T lymphocyte responses being very long lived. Additionally, ISCOMATRIX adjuvant can be used in vaccines for induction of mucosal immune responses. This review provides an overview of the immune responses that can be elicited using ISCOMATRIX vaccines and the current state of knowledge regarding the mechanism of action of this adjuvant.