Aerosolized antibiotics have the potential to deliver medications directly to the location of a lung infection while causing minimal systemic adverse effects. Understanding the factors of pharmacokinetics and drug deposition in the lung has allowed for the administration of high antibiotic concentrations in the lung. The current review includes pharmacokinetic and scintigraphic deposition investigations on aerosolized antibiotics that have been conducted experimentally and clinically. The practical deployment of various aerosolization systems for administration to patients breathing spontaneously or undergoing mechanical ventilation is discussed. Current clinical indications in patients with cystic fibrosis, bronchiectasis, and ventilator-associated pneumonia are reviewed, as well as future development prospects for this attractive mode of antibiotic treatment.