The concept of harnessing the immune system through vaccination traces back to Jenner's landmark observations on smallpox in the late 18th century. While infectious disease vaccines have since saved countless lives by priming protective immune responses, the underlying principle — educating T cells to recognize specific targets — is now being repurposed in entirely new directions. This applies in particular to personalized vaccines to fight cancer. Tumor neoantigens, arising from somatic mutations unique to each patient's malignancy, represent ideal targets for precision immunotherapy. While the concept is not new — the first neoantigen was discovered as early as 1988 — a breakthrough has now been reached through improved vaccine formulations and antigen discovery methods. Recent clinical validation includes the KEYNOTE-942 trial, in which an LNP-mRNA neoantigen vaccine sustained a 49% reduction in melanoma recurrence over five years. Neoantigen-derived peptide vaccines formulated with the adjuvant combination XS15/Montanide ISA 51 have likewise been shown to elicit robust, tumor-reactive T cell responses in cancer patients. In the context of the T-MoVac program, this potent combination is employed to treat late-stage sarcoma patients. Looking beyond oncology, a conceptually inverted application is the use of tolerogenic vaccine frameworks to induce regulatory or suppressive T cell responses for the treatment of autoimmune diseases and allergies. Emerging strategies in this space suggest that antigen-specific tolerance — rather than broad immunosuppression — may offer a safer and more durable therapeutic path. Together, these advances redefine vaccination as a tuneable platform for precisely modulating T cell immunity across a spectrum of human disease.