The coexistence of left- and right-handers is documented since prehistoric times, in all current ethnic groups, with some geographical frequency variations. Hand preference is influenced by genetic, hormonal, developmental, and cultural factors. Overall handedness is heritable, suggesting that this trait could evolve. Neutral models of evolution seem inadequate, as the generally low frequency of left-handers suggests some evolutionary costs. Data have suggested that left-handedness, as the rare hand preference, could represent an important strategic advantage in fighting interactions. The persistence of the polymorphism could thus be maintained by negative frequency-dependent selection. This fighting hypothesis, explaining the persistence of left-handers, applies only to situations where fighting abilities are directly linked to success (as in sports) or to Darwinian fitness, as in most past societies or in the few remaining groups not yet affected by Western colonization and a market economy. How the handedness polymorphism will evolve under the new modern conditions remains an interesting issue.