Asthma is characterized by a variable airway obstruction, bronchial hyperresponsiveness and airway inflammation. Usually, bronchial hyperresponsiveness is measured in the clinic by provocation with non specific stimuli such as histamine or methacholine. These stimuli are called direct, as they constrict the airways by a direct stimulation of airway smooth muscle. Pharmacological stimuli such as adenosine, tachykinins and bradykinin, and physical stimuli such as exercise, isocapnic hyperventilation or hypertonic saline, are called indirect stimuli: they stimulate inflammatory cells and/or neuronal cells and the released mediator and/or neurotransmitter causes the airways to narrow. In the past 10 years the mechanisms and receptors involved in the airway narrowing caused by these indirect bronchial challenges have been characterized. It has become clear that indirect challenges form a specific group of challenges that play a role in the diagnosis and the monitoring of asthma.