Targeting vaccines to the skin epidermis results in the activation of an immune inductive site that is rich in antigen-presenting cells. The superficial location of the skin makes it accessible to vaccine delivery. However, it is difficult to access the epidermis using needle and syringe delivery, and vaccine antigens are too large to be effectively delivered using standard topical formulations. Needle-free vaccine delivery systems have been developed for efficient delivery of particulate vaccines into the epidermal tissue. Particle-mediated epidermal delivery of DNA vaccines is based on the delivery of DNA-coated gold particles directly into the cytoplasm and nuclei of living cells of the epidermis, facilitating DNA delivery and gene expression. Alternatively, protein vaccines can be formulated into a dense powder, which can be propelled into the skin epidermis by epidermal powder immunisation using similar delivery devices and principles, but in this instance the protein is delivered to the extracellular space. Preclinical and clinical data will be reviewed, demonstrating applications of epidermal vaccine delivery to a wide range of experimental infectious disease vaccines.