The goals for the development of multiple antigen peptides (MAP) are to provide a rational and unambiguous system to multimerize different types of synthetic peptide antigens and to attach immunomodulating molecules for targeting and delivery. These goals have been largely realized and new designs of MAPs now permit a broad range of immune responses including CTLs and mucosal IgAs. Furthermore, significant advances by the inventiveness of many laboratories have led to applications of MAPs for serodiagnostic and other biochemical uses including those for drug discovery. An important aspect to accomplish various goals of MAPs is chemistry. New methodologies using unprotected peptides as building blocks have been developed to accommodate new and sophisticated design of MAPs. This review is written based on the personal perspective of my laboratory and will focus on the recent progress in MAPs, together with the chemistry to achieve their synthesis.