Coxiella burnetii is an obligate intracellular bacterium that causes a worldwide zoonotic disease, Q fever. Since C. burnetii infection is an occupational hazard and could develop into severe chronic disease in humans, vaccination should be considered to protect individuals at-risk of contact with naturally infected animals or exposure to the agents. Although several vaccines produced from Phase I whole-cell C. burnetii are effective in protecting against the infection in humans, vaccination of previously sensitized people can induce severe local and occasional systemic reactions. Safe use of these vaccines requires screening of potential vaccinees by skin tests, serological tests, or in vitro lymphocyte proliferation assay. Since these procedures are time-consuming and costly, they limit the use of whole-cell vaccines in a mass vaccination program. Efforts have been underway to develop a safer, more effective new-generation vaccine that will not cause adverse reactions when given to someone with pre-existing immunity. This article describes new information relating to the characterization of acquired immunity to C. burnetii infection that will provide a fundamental understanding of the development of protective immunity against Q fever. Recent works focused on development of recombinant vaccines against this pathogen offers promise in the pursuit of a new Q fever vaccine.