Frequency-dependent selection is an important process in the maintenance of genetic variation in fitness. In humans, it has been proposed that the polymorphism of handedness is maintained by negative frequency-dependent selection, through a strategic advantage of left-handers in fighting interactions. Using simple mathematical models, we explore: (1) whether it is possible to predict the range of left-handedness frequencies observed in human populations by the frequency and the violence of fighting interactions; (2) the consequences of the sex differences in the probability of transmission of hand preference to offspring. We show that a wide range of values of the frequency of left-handers can be obtained with realistic changes of the parameters values. Our models reinforce the idea that negative frequency-dependence may have played a role in maintaining left-handedness in human populations, and provide further support for the importance of fighting interactions in the evolution of hand preference. Moreover, they suggest an explanation for the occurrence of left-handedness among women in this context, namely an indirect selective advantage through their male offspring.