This Review deals with recent progress in the immunotherapy of established (pre)malignant disease of viral or non-viral origin by synthetic vaccines capable of inducing robust T-cell responses. The most attractive vaccine compounds are synthetic long peptides (SLP) corresponding to the sequence of tumour viral antigens or tumour-associated non-viral antigens. Crucial to induction of therapeutic T-cell immunity is the capacity of SLP to deliver specific cargo to professional antigen-presenting cells (dendritic cells (DC)). Proper DC activation then induces the therapeutic CD4+ and CD8+ T-cell responses that are associated with regression of established (pre)malignant lesions, including those induced by high-risk human papilloma virus.