Lipopeptides incorporating epitopes for CD4+ T cells and either CD8+ T cells or B cells have proven to be immunogenic in animal models and in humans and are well tolerated in these species. This form of vaccine candidate has great benefits over competing technology in terms of providing a totally synthetic and pure product that is effective when administered in the absence of any adjuvant, and is immunogenic when delivered by a variety of routes, including application to mucosal surfaces. The immune response can be focused on critical epitopes of the pathogen or tumour antigen to provide clearing immunity, and responses can also be invoked that modulate hormone activity. This review will cover examples of lipopeptides of different design and their efficacy in different systems as well as challenges for the future. Our recent understanding of how the lipid component confers the "self-adjuvanting" property on these immunogens by targeting the cell at the heart of immune response induction, the dendritic cell, will also be discussed.