Recognition of the importance of breathing pattern in aerosol delivery and deposition has led to the design of devices that allow targeting of deposition to airways and alveoli. Systems incorporating patient feedback provide control of factors affecting deposition, and the control of dose to the lung can now be expected. New devices combined with a medical realization of therapeutic need are beginning to affect the range of drugs now available to the caregiver or in development for the immediate future. The interface between the patient and the device represents a new area of practical research. Facemasks have been shown to be important in terms of drug delivery with different behavior in metered dose inhaler (MDI)/valved holding chambers compared to nebulizers. Recently completed clinical trials have demonstrated the usefulness of therapy targeted to the lungs in reducing systemic toxicity with enhanced efficacy. A prime example is aerosolized cyclosporine, used to prevent rejection in lung transplantation. This agent has recently been shown to reduce mortality in transplant recipients and will lead to a new drug application in the United States. For larger patient populations, the pursuit of therapies to reduce the incidence of ventilator-associated pneumonia (VAP) can affect the outcome of illness in the intubated patient in the Intensive Care Unit (ICU). Patients with idiopathic pulmonary fibrosis (IPF) may benefit from high doses of aerosolized interferon gamma. Patient and caregiver safety are additional factors that will affect future approaches to therapy.