Handedness is the preference shown by children and adults for left versus right hand use in unimanual tasks. A variety of questionnaires have been developed to measure such preference, with the Edinburgh Handedness Inventory being the most famous and widely employed. Handedness is important in that it serves as a potential neuropsychological marker of underlying brain development and may also reflect the manner in which cognitive functions are localized to the left or right cerebral hemispheres. This proposed link between brain function and hand dominance raises a question of particular interest: namely, whether hand preference systematically relates to individual differences in intellectual abilities and/or talents. Lefthanders do less well than right-handers on the performance component of the Wechsler Adult Intelligence Scale (WAIS) and slightly better than right-handers on the verbal component. The chapter considers several factors that may serve to moderate the relationship between handedness and intellectual ability. Of all the variables that moderate the relationship between hand dominance and ability, the strength of handedness and familial sinistrality (FS) have probably received the most attention. FS, in the most general sense, refers to individuals who have left-handed or ambidextrous relatives. It is found that moderately strong left- and right-handed subjects with a positive history of FS (FS +) had slightly lower WAIS IQ scores than left- and right-handers with no evidence of FS (FS -).