Synthetic vaccines, in particular long synthetic peptides of approximately 25-50 amino acids in length, are attractive for HIV vaccine development and for induction of therapeutic immune responses in patients with (pre-)malignant disorders. In the case of preventive vaccine development against HIV, no major success has been achieved, but the possibilities are by no means exhausted. A long peptide vaccine consisting of 13 overlapping peptides, which together cover the entire length of the two oncogenic proteins E6 and E7 of high-risk human papilloma virus type 16 (HPV16), caused complete regression of all lesions and eradication of virus in 9 out of 20 women with high-grade vulvar intraepithelial neoplasia, a therapy-resistant preneoplastic disorder. The nature and strength of the vaccine-prompted T cell responses were significantly correlated with the clinical response. Synthetic peptide vaccines are attractive, because they allow rational improvement of vaccine design and detailed pharmacokinetic and pharmacodynamic studies not possible with conventional vaccines. Improvements are possible by addition or conjugation of adjuvants, notably TLR ligands, to the synthetic peptides.