Although atrial fibrillation is a very common medical problem in general population and has a high incidence in the setting of open heart surgery, currently there are very few therapies to prevent occurrence or recurrence of atrial fibrillation. N-3 polyunsaturated fatty acids have been shown to change basic physiologic properties of the atrial tissue to make it less susceptible to atrial fibrillation. In this review, we first describe basic physiological mechanisms thought to be responsible for these changes and then discuss epidemiological studies evaluating the use n-3 polyunsaturated fatty acids for primary and secondary prevention of atrial fibrillation in the general population, in subjects undergoing open heart surgery, and in special subgroups of patients.