Conventional vaccine adjuvants enhance peptide-specific T-cell and B-cell responses by modifying peptide stability or uptake or by binding to pattern-recognition receptors on antigen-presenting cells (APCs). This article discusses the application of a distinct mechanism of adjuvant activity: the activation of type I, or invariant, natural killer T (iNKT) cells to drive cellular and humoral immune responses. Using a semi-invariant T-cell receptor (TCR), iNKT cells recognize glycolipid antigens presented on cluster of differentiation (CD)-1d molecules. When their ligands are presented in concert with peptides, iNKT cells can provide T-cell help, ‘licensing’ APCs to augment peptide-specific T-cell and antibody responses. We discuss the potential benefits and limitations of exploiting iNKT cells as ‘universal helpers’ to enhance vaccine responses for the treatment and prevention of cancer and infectious diseases.