Combining drug therapies for dual infection by Mycobacterium tuberculosis and HIV-1 is made complex by high pill burdens, shared drug toxicities, drug-drug and drug-disease interactions, immune reconstitution inflammatory syndrome, co-morbid diseases and drug resistance in both bacillus and virus. Recently, novel anti-tubercular and anti-retroviral drugs have bolstered the tuberculosis-HIV drug pipelines and may help ameliorate these difficulties. This review article discusses the reasons for current problems of therapy for dual infection. It also identifies promising agents, which may significantly improve co-therapy and thus diminish the great morbidity and mortality of these two pandemics.