The skin provides an attractive immune environment for vaccine delivery and a safe and confined anatomic space for the use of potent adjuvants. It has been presumed that LCs as a class of dendritic cells should stimulate potent immune responses when activated by adjuvants, and this theory is beginning to be validated. Progress on simple pretreatment of the skin has led to well-developed, simple-to-use protocols that are not dissimilar from current protocols used to cleanse the skin before injection. Antigen and adjuvant formulation optimization has progressed, leading to phase 2 testing of the technology in formulated, manufacturable patches. Although delivery optimization and product testing is challenging, the major biologic observations underlying TCI and the IS patch have been established clearly in that large protein antigens have been delivered clinically, resulting in robust immune responses in a safe manner. During the next 5 years, the challenge will be to conduct a development program that leads to safe and effective vaccination in the context of specific applications.