This manuscript describes the design of new vaccines based on synthetic peptides. To this end, we first analyze the structural basis of antigenic reactivity and specificity and the various types of epitopes that form the mosaics of macromolecular antigens, as well as the regulatory mechanisms involved in immune recognition. A distinction is made between sequential or continuous epitopes, and discontinuous or conformational ones, which are the majority of epitopes in globular proteins. In this context it is of particular interest to identify epitopes reacting with B cells and T cells, respectively, or with cytotoxic T cells, in association with the major histocompatibility cell-surface antigens, and the role of these interactions in protective immunity. Identification of such epitopes in proteins of viral, bacterial, or parasitic organisms led to the synthesis of peptides, which when used in conjunction with appropriate carriers and/or adjuvants induced neutralizing antibodies. Particular examples are described, including: bacterial epitopes and mainly those of toxins of diphtheria, cholera, and shigella, leading not only to neutralizing antibodies but also to protective immunity against the deleterious effects of the respective toxins; parasite epitopes, such as those leading to anti-malaria vaccine, based on either the sporozoite or the merozoite stage antigens; viral epitopes leading to protective immunity, with special emphasis on influenza virus where induction of CTL is crucial; and finally, synthetic peptide vaccines against HIV, which should lead to broad specificity protective immunity while avoiding the risks of a vaccine based on the infectious agent. The rapid recent progress in this field, as described in this review, increases the prospect of constructing successful synthetic peptide vaccines in the not too distant future.