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This paper reviews the history of aerosol therapy; discusses patient, drug, and device factors that can influence the success of aerosol therapy; and identifies trends that will drive the science of aerosol therapy in the future. Aerosol medication is generally less expensive, works more rapidly, and produces fewer side effects than the same drug given systemically. Aerosol therapy has been used for thousands of years by steaming and burning plant material. In the 50 years since the invention of the pressurized metered-dose inhaler, advances in drugs and devices have made aerosols the most commonly used way to deliver therapy for asthma and COPD. The requirements for aerosol therapy depend on the target site of action and the underlying disease. Medication to treat airways disease should deposit on the conducting airways. Effective deposition of airway particles generally requires particle size between 0.5 and 5 m mass median aerodynamic diameter; however, a smaller particle size neither equates to greater side effects nor greater effectiveness. However, medications like peptides intended for systemic absorption, need to deposit on the alveolar capillary bed. Thus ultrafine particles, a slow inhalation, and relatively normal airways that do not hinder aerosol penetration will optimize systemic delivery. Aerosolized antimicrobials are often used for the treatment of cystic fibrosis or bronchiectasis, and mucoactive agents to promote mucus clearance have been delivered by aerosol. As technology improves, a greater variety of novel medications are being developed for aerosol delivery, including for therapy of pulmonary hypertension, as vaccines, for decreasing dyspnea, to treat airway inflammation, for migraine headache, for nicotine and drug addiction, and ultimately for gene therapy. Common reasons for therapeutic failure of aerosol medications include the use of inactive or depleted medications, inappropriate use of the aerosol device, and, most importantly, poor adherence to prescribed therapy. The respiratory therapist plays a key role in patient education, device selection, and outcomes assessment.