Increasing antibiotic resistance and lack of R&D productivity of new classes of antimicrobial agents directed against Gram-negative bacteria necessitate new approaches to maximize the efficacy of existing classes of drugs. Direct administration of drugs to the lung via the inhalational route provides for high concentrations at the target site of action in patients with pulmonary infections. The efficacy of aerosol antibiotic administration has been best demonstrated with aerosolized tobramycin in the management of chronic infections because of Pseudomonas aeruginosa in cystic fibrosis (CF) patients. Unfortunately, inconvenient regimens leading to poor patient adherence to therapy, and the increasing frequency of multidrug-resistant strains have necessitated the search for additional agents. Integration of aerosol science, PK-PD and clinical trial designs are important for the development and evaluation of these new aerosol agents in both chronic infections (e.g. CF and chronic obstructive pulmonary disease (COPD)) as well as acute infections (e.g. bacterial pneumonias). This review outlines important considerations and recent progress in this emerging area.