The neuronal correlates of handedness are still poorly understood. Here we used event-related functional magnetic resonance imaging to investigate the impact of handedness on neuronal activation of the primary sensorimotor cortex, supplementary motor area and dorsal premotor cortex during simple unilateral and bilateral finger movements. In 16 right-handed and 16 left-handed individuals, we mapped changes in regional neuronal activity while participants responded to four symbolic cues presented in a pseudorandom order. According to pre-specified cues, they pressed a button with their right, left or both index fingers or withheld a response. For unilateral right index finger button presses, reaction times, motor and premotor activity were the same for both right- and left-handers. Compared with right-handers, left-handers had shorter reaction times with unilateral left index finger button presses, along with greater activation of the supplementary motor area and right frontal opercular cortex. Simultaneous bilateral compared with unilateral button presses led to a relative increase of activity in the right and left dorsal premotor cortex and the right primary sensorimotor cortex in right but not left-handers. Neither right nor left-handers showed any tendency during bilateral button presses towards faster responses with the dominant hand and the reaction times were equal in the two groups. Therefore, we conclude that the relative increase of activity in dorsal premotor and right primary sensorimotor cortices in right-handers represents a genuine difference in bimanual motor control related to handedness.