Bacterial respiratory diseases remain a major cause of morbidity and mortality throughout the world. The young and the elderly are particularly susceptible to the pathogens that cause these diseases. Therapeutic approaches remain dependent upon antibiotics contributing to the persistent increases in antibiotic resistance. The main causes of respiratory disease discussed in this review are Mycobacterium tuberculosis, Corynebacterium diphtheriae, Bordatella pertussis, Streptococcus pneumoniae, non-typeable Haemophilus influenzae, Moraxella catarrhalis and Pseudomonas aeruginosa. All these organisms initiate disease at the mucosal surface of the respiratory tract and thus the efficacy of the host's response to infection needs to be optimal at this site. Vaccines available for diseases caused by many of these pathogens have limitations in accessibility or efficacy, highlighting the need for improvements in approaches and products. The most significant challenges in both therapy and prevention of disease induced by bacteria in the respiratory tract remain the development of non-injectable vaccines and delivery systems/immunization regimens that improve mucosal immunity.