Botulism is a severe neuroparalytic disease caused by the toxins produced from several Clostridium species. Botulinum neurotoxins (BoNTs) cause flaccid paralysis by inducing a blockade at voluntary motor and autonomic cholinergic junctions that, if not treated, can be fatal. Vaccination to elicit protective circulating antibodies that bind, neutralize and clear toxins before they can be internalized and affect cholinergic neurons remains the most effective form of protection against BoNT. A pentavalent BoNT toxoid vaccine administered in the USA under an Investigational New Drug protocol to at-risk workers was discontinued by the CDC in 2011 due to diminished potency and reactogenic effects. Subsequent research efforts have primarily focused on recombinant protein antigens. This review focuses on the development of a recombinant bivalent vaccine (rBV A/B) composed of purified recombinant BoNT/A and BoNT/B receptor-binding domain proteins, as well as presenting a summary of progress and issues associated with alternative vaccines currently being developed against botulism.