Musicians not only have extraordinary motor and sensory skills, but they also have an increased ability to learn new tasks compared with non-musicians. We examined how these features are expressed in neurophysiological parameters of excitability and plasticity in the motor system by comparing the results of 11 professional musicians and 8 age-matched non-musicians. Parameters of motor excitability were assessed using transcranial magnetic stimulation (TMS) to measure motor-evoked potentials (MEPs) together with recruitment of corticospinal projections [input-output curve (IOcurve)] and of short-latency intracortical inhibition (SICIcurve). Plasticity, here defined as change of synaptic effectiveness, was tested by measuring MEPs and IOcurves after paired associative stimulation (PAS), which consists of an electric median nerve stimulus repeatedly paired (200 times at 0.25 Hz) with a TMS pulse over the hand motor area. Using an interstimulus interval of 25 ms (PAS25) or 10 ms (PAS10), this leads to long-term potentiation- or long-term depression-like plasticity, respectively. Musicians showed steeper recruitment of MEPs and SICI (IOcurve and SICIcurve). Additionally, PAS25 increased and PAS10 decreased the MEP amplitudes and the slope of the IOcurves significantly more in musicians than in non-musicians. This is consistent with a wider modification range of synaptic plasticity in musicians. Together with the steeper recruitment of corticospinal excitatory and intracortical inhibitory projections, this suggests that they regulate plasticity and excitability with a higher gain than normal. Because some of these changes depend on age at which instrumental playing commenced and on practice intensity, they may reflect an increase in number and modifiability of synapses within the motor area caused by long-term musical practice.