Counter-regulatory lipid mediators are generated during airway inflammation to promote resolution. Defects in the production of these lipid mediators have now been associated with several diseases of persistent airway inflammation. Lipoxins are the lead members of this class of anti-inflammatory and proresolving chemical mediators. Recently, several new families of fatty acid-derived counter-regulatory mediators have been discovered, including the resolvins and protectins. Diminished formation of these endogenous protective signals would interrupt the natural resolution of inflammation. Here, we review how rapidly emerging information on lipoxins, resolvins and protectins is providing new insights into the pathophysiology of chronic airway inflammation in several common illnesses, including asthma.