The idea that handedness indicates something about a person's cognitive ability and personality is a perennial issue. A variety of models have been put forward to explain this relationship and predict a range of outcomes from higher levels of cognitive ability in left-handers or moderate right-handers to lower levels of achievement in left- or mixed-handers. We tested these models using a sample (n = 895) drawn from the BRAINnet database (www.brainnet.net). Participants completed a general cognitive ability (GCA) scale and a test of hand preference/performance. Moderate right-handers, as indexed by their performance measures, had higher GCA scores compared with strong left- or right-handers. The performance measure also showed lower levels of GCA for left-handers compared with right-handers. The hand preference data showed little or no association with cognitive ability-perhaps because this measure clusters individuals toward the extremes of the handedness distribution. While adding support to Annett's heterozygous advantage model, which predicts a cognitive disadvantage for strong left- or right-handers, the data also confirm recent research showing a GCA disadvantage for left-handers. Although this study demonstrates that handedness is related to cognitive ability, the effects are subtle and might only be identified in large-scale studies with sensitive measures of hand performance.