The multi-stage cascade impactor is the mainstay methodology for the determination of aerodynamic particle size distribution (APSD) of aerosols emitted by Inhalation Aerosols and Sprays, and Inhalation Powders, as described in Inhalation and Nasal Drug Products: Aerosols, Sprays, and Powders—Performance Quality Tests 〈601〉. This equipment is also recommended for APSD assessment associated with the use of drug products dispersed by nebulizing systems in Products for Nebulization—Characterization Tests 〈1601〉 as well as for the assessment of add-on devices for use with inhalation aerosols in Spacers and Valved Holding Chambers Used With Inhalation Aerosols—Characterization Tests 〈1602〉. Both chapters provide instructions on how to determine APSD, but due to necessity are focused on the measurement process itself, and are therefore limited in the advice given to assist in obtaining consistent measurements by these apparatuses. The cascade impactor is a complex apparatus to set-up, use, and maintain correctly. This chapter provides guidance to optimize the accuracy and precision of the methods described in 〈601〉, 〈1601〉, and 〈1602〉 for the determination of APSD.