The success of inhalation therapy is not only dependent upon the pharmacology of the drugs being inhaled but also upon the site and extent of deposition in the respiratory tract. This article reviews the main mechanisms affecting the transport and deposition of inhaled aerosol in the human lung. Aerosol deposition in both the healthy and diseased lung is described mainly based on the results of human studies using nonimaging techniques. This is followed by a discussion of the effect of flow regime on aerosol deposition. Finally, the link between therapeutic effects of inhaled drugs and their deposition pattern is briefly addressed. Data show that total lung deposition is a poor predictor of clinical outcome, and that regional deposition needs to be assessed to predict therapeutic effectiveness. Indeed, spatial distribution of deposited particles and, as a consequence, drug efficiency is strongly affected by particle size. Large particles (>6 μm) tend to mainly deposit in the upper airway, limiting the amount of drugs that can be delivered to the lung. Small particles (<2 μm) deposit mainly in the alveolar region and are probably the most apt to act systemically, whereas the particle in the size range 2-6 μm are be best suited to treat the central and small airways.