There are several different types of drug delivery interfaces available on the market. Using the right interface for aerosol drug delivery to children is essential for effective inhalation therapy. However, clinicians usually focus on selecting the right drug-device combination and often overlook the importance of interface selection that lead to suboptimal drug delivery and therapeutic response in neonates and pediatrics. Therefore, it is necessary to critically assess each interface and understand its advantage and disadvantages in aerosol drug delivery to this patient population. The purpose of this paper is to provide a critical assessment of drug delivery interfaces used for the treatment of children with pulmonary diseases by emphasizing advantages and problems associated with their use during inhalation therapy.