Technical Abstract: Since its early development more than two hundred years ago, vaccination has become one of the most effective measures to prevent infectious diseases. The use of vaccines is responsible for global eradication of smallpox and also for saving millions of human lives that otherwise would have been lost or severely impaired due to diseases such as polio, tetanus and measles, among others. An ideal vaccine should: (A) elicit long lasting protective immunity, preferably soon after its administration, without causing disease in the recipient or subsequent contacts, (B) allow detection of infected vs. immunized individuals without interfering with available diagnostic tests, (C) be cost effective and easy to produce in large quantities, (D) be easy to store and transport preserving its immunobiological properties under different environmental conditions, (E) be easy to administer to large populations, ideally in a single dose, without causing side effects, (F) be safe enough to be used in immunocompromised hosts, (G) have therapeutic potential and (H) be compatible with other vaccines so they can be administered simultaneously without interfering with each other’s effectiveness and safety. Additionally, consideration should be given to the different environments and societies in which the vaccine must be administered, since those factors will directly affect individual’s compliance with any proposed immunization regimen. This chapter reviews how DNA vaccines fare against these criteria in preventing tuberculosis.