Inhalation of drug aerosols is a modern pathway to combat lung diseases. It is also becoming the preferred route for insulin delivery, pain management, cancer therapy, and nanotherapeutics. Popular delivery devices include nebulizers, metered-dose inhalers, and dry-powder inhalers. They are all nondirectional and hence have typically low particle deposition efficiencies in desired nasal or lung areas. Thus, for specific disease treatment with costly and/or aggressive medicine, it is necessary to provide targeted drug-aerosol delivery to predetermined sites in the human respiratory system. Experimental measurements and computer models of particle transport and deposition in nasal and lung airway models are presented. Furthermore, the underlying methodology and performance of pressurized metered dose inhalers as well as new smart inhaler systems are discussed. To maximize respiratory drug delivery to specific sites, an optimal combination of particle characteristics, inhalation waveform, particle release position, and drug-aerosol dosage has to be achieved.