Neuropsychological and neuroimaging evidence convincingly implicates the left cerebral hemisphere in the representation of skilled movements (praxis) in right-handers. Compelling and consistent data on the organization of praxis in left-handed individuals has only recently started to emerge. This new evidence, again both from neuropsychology and neuroimaging, supports the notion that in left-handers the neural substrate of praxis skills is less asymmetric, i.e., it is more bilaterally organized. Up until recently, though, the neuropsychological literature on brain-damaged left-handers was often dominated by descriptions of more or less atypical cases and dissociations of functions observed in such individuals. Associations of deficits, linked to anatomic proximity rather than to a common cerebral specialization, were rarely found worth publishing and/or in-depth discussions. This paper first reviews some of the most relevant and/or well-known reports on representations of different categories of skilled manual gestures in right- and left-handers, with a view to support the idea that these skills are mediated by a common system. Then, based on neuroimaging evidence from healthy subjects, a few individuals with unusual organization of praxis are discussed. These disparate cases quite likely represent natural variation in functional asymmetries. It is yet to be determined whether the effect of a more bilateral organization of cognitive skills in this population is just due to a much higher incidence of atypical representations of functions or rather a general tendency for all left-handers to have their brains less asymmetrically organized.