Infants have low tidal volume, vital capacity, and functional residual capacity, and short respiratory cycles (low I:E ratio), which result in a low residence time for aerosol particles and, thus, low pulmonary deposition of aerosol particles (< 1% of the nominal dose), compared to adults (8-22%). Scintigraphy data suggest aerosol deposition of < 1% in both intubated and nonintubated infants. In vitro testing appears to overestimate pulmonary deposition, partly because in vitro testing does not account for exhaled aerosol. Animal models of infant ventilation tend to agree with data from human studies. However, though only a small percentage of the aerosol deposits in the lung, infants nevertheless receive considerably more aerosolized drug per kilogram of body weight than do adults. Efficient aerosol delivery to infants is challenging because of low deposition and high inter-patient and intra-patient variability, but existing systems can effectively delivery various aerosolized drugs, including bronchodilators, anti-inflammatories, and anti-infectives. Use of a nebulizer that has a low residual volume (of drug remaining in the device after nebulization) delivers up to 13%. Awareness of the variables that impact aerosol delivery efficiency can result in more effective treatment of mechanically ventilated infants.