The topical distribution of inhaled therapies in the lung can be viewed using radionuclides and imaging. Positron emission tomography (PET) is a three-dimensional functional imaging technique providing quantitatively accurate localization of the quantity and distribution of an inhaled or injected PET radiotracer in the lung. A series of transaxial slices through the lungs are obtained, comparable to an X-ray computed tomography (CT) scan. Subsequent reformatting allows coronal and sagittal images of the distribution of radioactivity to be viewed. This article describes procedures for administering [(18)F]-fluorodeoxyglucose aerosol to human subjects for the purpose of determining dose and distribution following inhalation from an aerosol drug delivery device (ADDD). The advantages of using direct-labeled PET drugs in the ADDD are discussed with reference to the literature. The methods for designing the inhalation system, determining proper radiation shielding, calibration, and validation of administered radioactivity, scanner setup, and data handling procedures are described. Obtaining an X-ray CT or radionuclide transmission scan to provide accurate geometry of the lung and also correct for tissue attenuation of the PET radiotracer is discussed. Protocols for producing accurate images, including factors that need to be incorporated into the data calibration, are described, as well as a proposed standard method for partitioning the lung into regions of interest. Alternate methods are described for more detailed assessments. Radiation dosimetry/risk calculations for the procedures are appended, as well as a sample data collection form and spreadsheet for calculations. This article should provide guidance for those interested in using PET to determine quantity and distribution of inhaled therapeutics.