Early clinical trials, in which over 1000 cancer patients received dendritic cell (DC) vaccines, tested different vaccine preparations, but they did not always induce sufficient acquired immunity or meet the expected level of tumor regressions. Current studies aim to improve the DC vaccine approach and capture the potential of these cells in order to gain access to lymphoid tissues and induce strong cell-mediated immunity. DC clinical trials are moving towards a more professional environment, in accordance with the latest quality standards. This explains the current need for innovative well designed trials with defined endpoints that induce robust anti-tumor immunity.