Macrophages exert prominent effects in the defense of the respiratory tract from airborne pathogens. These cells are specialized to recognize, phagocytose, and destroy these infectious agents and then promote appropriate tissue repair after successful pathogen clearance. For reasons that are not presently clear, macrophages appear to be inappropriately activated during asthma responses. Evidence stems from the appearance of either classically (or M1) and alternatively activated (or M2) cells in the alveolar compartment of asthmatic lung. Macrophages localized in the interstitial area of the lung appear to be less prone to polarization toward either the M1 or M2 phenotype as these cells predominately express interleukin-10 and exhibit immunoregulatory properties. Effective treatment of clinical asthma, regardless of severity, might depend on restoring an appropriate balance between M1, M2, and immunoregulatory macrophages in the lung.