Abstract Experimental results consistently show that the respiratory control system is plastic, such that environmental factors and experience can modify its performance. Such plasticity may represent basic neurobiological principles of learning and memory, whereby intermittent sensory stimulation produces long-term alterations (i.e. facilitation or depression) in synaptic transmission depending on the timing and intensity of the stimulation. In this review, we propose that intermittent chemosensory stimulation produces long-term changes in respiratory motor output via specific neuromodulatory systems. This concept is based on recent data suggesting that intermittent hypoxia produces a net long-term facilitation of respiratory output via the serotonergic system, whereas intermittent hypercapnia produces a net long-term depression by a mechanism associated with the noradrenergic system. There is suggestive evidence that, although both respiratory stimuli activate both modulatory systems, the balance is different. Thus, these opposing modulatory influences on respiratory motor control may provide a ‘push–pull’ system, preventing unchecked and inappropriate fluctuations in ventilatory drive.