Spacers and valved holding chambers (VHCs) overcome common problems experienced by patients with use of pressurized metered-dose inhalers (pMDIs), namely difficulty in coordinating inhalation with the high velocity spray emitted by pMDIs and high oropharyngeal deposition of inhaled corticosteroids in some patients. Spacers/VHCs reduce aerosol velocity and VHCs retain the aerosol cloud in the chamber allowing patients time to inhale slowly and deeply. Aerosol retention within a VHC produces a finer aerosol due to partial propellant evaporation and impaction of large particles on chamber walls and valve. Various design factors, such as spacer volume, shape, valve design, the level of electrostatic charge accumulating on the spacer inner surfaces, and the interface employed (facemask or mouthpiece), as well as use of multiple actuations and delay between actuation and inhalation influence the dose delivered from a spacer or VHC. Likewise, patient-related factors, such as age, breathing pattern (tidal volume and inspiratory airflow), coordination with pMDI actuation, and presence of airflow obstruction determine clinical responses to drugs administered with a spacer/VHC and pMDI. Appropriate education and training avoid common patient errors while using spacers/VHCs. Spacers or VHCs significantly alter the aerosol characteristics and dose of drug delivered to the patient by pMDIs; moreover, pMDIs and spacers/VHCs are not interchangeable. Use of spacers/VHCs with pMDIs could benefit infants, children <5 years of age, elderly and frail individuals who are unable to coordinate inhalation with pMDI actuation, those with compromised comprehension or manual dexterity, and those experiencing acute attacks of asthma or COPD. This chapter discusses the design, properties, and function of a number of spacers and valved holding chambers (VHCs). It describes the differences between products and the many factors and outcome measures that should be considered when choosing a spacer/VHC for patients. The design of spacers and VHCs employ 3 basic concepts, the open tube design, the reservoir or holding chamber design, and the reverse-flow design, in which the pressurized metered-dose inhalers (pMDIs), placed close to the mouth, is fired in the direction away from the patient. Aerosols emitted from pMDIs have an intrinsic electrostatic charge which varies with different formulations. pMDIs and VHCs are convenient for administering bronchodilators to infants and children, and to adults during acute exacerbations of asthma or chronic obstructive pulmonary disease. Several systematic reviews and meta-analyses have concluded that administration of bronchodilators with a pMDI and VHC combination is equally effective as a nebulizer or dry powder inhalers in both children and adults with acute asthma.