Brucellosis, an infection caused by Brucella spp., is a common zoonosis in many parts of world. Human chronic infection is successfully established through contact with infected animals or their dirty products. The capacity of establishing and maintaining this persistent infection in the phagosomal compartment of host macro-phages is critical to their ability to produce chronic infections in their mammalian hosts. Bacterial virulence mechanisms play an important role in regulating during the infectious process, both to optimize the functioning of the virulence factors in promoting survival and thwarting host defenses and to produce an effective immune response against these virulence components. The availability of the genomic sequences and molecular strategies such as gene mutant technique provide an opportunity to identify the virulence mechanisms of Brucella. It will greatly accelerate our understanding of the infection of this pathogen and give us more clues to exploit new vaccines and drugs.