Early studies of the use of antibiotics in patients with cystic fibrosis suggested that they would be of benefit in preventing or reducing infection by Pseudomonas aeruginosa. In seeking to optimize treatment, factors such as the drug used, the dose, the regimen and the formulation must be considered. Aminoglycosides are ideal for aerosolization because they have a long post-antibiotic effect and have an acceptable taste. Tobramycin is one of the aminoglycosides with the lowest systemic toxicity, which enables the aerosol delivery of doses high enough to overcome the antagonistic effects of the sputum. The most dramatic benefits from inhaled tobramycin have been shown to occur in the first 2-4 weeks of administration. Continual administration for longer periods can result in the development of resistance and loss of the improvement in lung function. However, this resistance is transient, and susceptibility to tobramycin returns after a short drug holiday. Optimal drug administration therefore consists of a 4-week on, 4-week off cycle. Such a cycle also helps to maintain patient compliance. Successful drug delivery also depends upon a formulation that does not provoke bronchoconstriction, which demands a formulation that is both preservative free, and osmotically and pH balanced. This research has enabled the development of a novel formulation of tobramycin optimized for use as an inhalation therapy in cystic fibrosis.