The field of melanoma immunobiology has made tremendous strides in the past decade, resulting in the molecular identification of a vast array of tumour-expressed antigens that contain determinants that are recognised by patient T cells or immunoglobulins. The integration of these antigens, their derivative peptides or improved analogues in vaccine trials allows for the augmentation of melanoma-specific CD4+ and CD8+ T cells in situ that may prove clinically efficacious in the adjuvant or therapeutic setting. Indeed, melanoma peptide-based immunotherapies targeting the activation of anti-tumour CD8+ cytotoxic T lymphocytes have proven successful (i.e. yielding objective clinical responses), particularly when combined with T cell growth factors or potent antigen-presenting cells, such as dendritic cells. Vaccine approaches implementing poly-epitope and/or melanoma peptides recognised by CD4+ T cells are anticipated to yield still better clinical outcomes due to the in vivo promotion and maintenance of a diversified, poly-specific effector T cell repertoire directed against resident tumours.