By default all characters are either right or left-hand dominant, and suffer a -3 penalty to any precision actions carried out with their offhand - such as one-handed Attacks.
Some weapons, typically those that are small and/or specially designed for offhand use, are easier to wield in the offhand and suffer from Reduced Offhand Penalty (-2) or even Minimal Offhand Penalty (-1). Unarmed attacks always qualify for Minimal Offhand Penalty. The Offhand Penalty can also be reduced by the Offhand Proficiency Ability.
For obvious reasons, characters that are Ambidextrous do not suffer from an Offhand Penalty.