Cytokine and cytokine antagonist have provided novel and effective therapies for many human diseases. A number of approved cytokines including the interferons (alpha, beta and gamma), interleukin-2 (IL-2), granulocyte macrophage colony stimulating factor (GM-CSF) as well as novel cytokine antagonists have been administered by the pulmonary route for both local lung disease and as a non-invasive method for systemic delivery. We review the published clinical experience of inhaled cytokines and cytokine antagonists. We discuss the limitations of the existing data and the type of clinical data desired to establish the advantages and safety of inhaled cytokines and cytokine antagonists.