Inhaled corticosteroids (ICSs) are the foundation of pharmacotherapy in persistent asthma because they control airway inflammation. The anti-inflammatory effect of ICSs is primarily topical, at their site of deposition in the airways. Consequently, deposition characteristics of the ICS and its formulation and inhalation device, in addition to intrinsic properties of the corticosteroid, influence clinical efficacy. Small-particle formulations, especially those developed in a metered-dose inhaler with the new hydrofluoroalkane propellant, may have improved lung deposition characteristics along with possibly improved clinical efficacy. Lipid conjugation of ICSs within the lungs may allow prolonged duration of effect, enabling once-daily dosing. Safety concerns of ICSs are related to systemic absorption and oropharyngeal deposition. An ICS with a longer serum half-life, especially one with a higher affinity for the corticosteroid receptor, may be associated with greater systemic effects. Increased protein binding of an ICS within the systemic circulation and high systemic clearance of an ICS may reduce the risk for systemic effects. Reduced oropharyngeal deposition and administration of a prodrug may result in fewer oropharyngeal side effects. The ideal ICS will have increased lung deposition and reduced deposition in the upper airway, resulting in better clinical efficacy and less risk for upper airway adverse effects. An ICS with high plasma protein binding and rapid clearance might pose much less risk for systemic adverse effects than currently available drugs in this class.