Infants and toddlers are a unique subpopulation with regard to aerosol therapy. There are various anatomical, physiological and emotional factors peculiar to this age group that present significant difficulties and challenges for aerosol delivery. Most studies on the factors determining lung deposition of therapeutic aerosols are based on data from adults or older children, which cannot simply be extrapolated directly to infants. The present review describes why infants/toddlers are very different with respect to two major issues - namely their anatomy/physiology and their behavior. We suggest possible solutions and future research directions aimed at improving clinical outcomes of aerosol therapy in this age group.