The global burden of human brucellosis remains enormous, yet its optimal treatment remains based on traditional combinations of doxycycline with either rifampicin or streptomycin. Of the currently existing alternative regimens, only the combination of doxycycline with gentamicin can be considered therapeutically adequate and cost effective, the latter factor being a major obstacle in the utilisation of quinolones for brucellosis. Newer antibiotics, most notably tigecycline, may help in achieving monotherapy or shorter treatment duration. Alternatively, modification of the acidic intracellular environment where Brucellae reside may allow for enhanced effectiveness of existing antibiotics.