Accumulating evidence has documented a role for B cells and antibodies (Abs) in the immunity against Mycobacterium tuberculosis (Mtb). Passive transfer studies with monoclonal antibodies (mAbs) against mycobacterial antigens have shown protection against the tubercle bacillus. B cells and Abs are believed to contribute to an enhanced immune response against Mtb by modulating various immunological components in the infected host including the T-cell compartment. Nevertheless, the extent and contribution of B cells and Abs to protection against Mtb remains uncertain. In this article we summarize the most relevant findings supporting the role of B cells and Abs in the defense against Mtb and discuss the potential mechanisms of protection.