Interactions between inhaled particles and the respiratory tract fluids are important for inhaled drug delivery systems. In particular, controlling the transport of aerosol particles after deposition in the respiratory tract may improve drug retention time in the lungs, allow targeting, and facilitate optimal transport through innate defense mechanisms of the lung. In this chapter the mechanisms by which particles can transport in the lungs and the aerosol design criteria for improving particle residence times or promoting uniform distribution across or within the lung space are discussed.