OBJECTIVE To assess the co-occurrence of fibromyalgia with psychiatric disorders in participants of a fibromyalgia family study. METHOD Patients (probands) with fibromyalgia, control probands with rheumatoid arthritis, and first-degree relatives of both groups completed a structured clinical interview and tender point examination. The co-occurrence odds ratio (OR) (the odds of a lifetime comorbid DSM-IV disorder in an individual with fibromyalgia divided by the odds of a lifetime comorbid disorder in an individual without fibromyalgia, adjusted for age and sex) was calculated; observations were weighted by the inverse probability of selection, based on the fibromyalgia status of the pro-band; and standard errors were adjusted for the correlation of observations within families. The study was conducted from September 1999 to April 2002. RESULTS We evaluated 78 fibromyalgia pro-bands and 146 of their relatives, and 40 rheumatoid arthritis probands and 72 of their relatives. Among the relatives of both proband groups, we identified 30 cases of fibromyalgia, bringing the total number of individuals with fibromyalgia to 108, compared with 228 without fibromyalgia. The co-occurrence ORs for specific disorders in individuals with versus those without fibromyalgia were as follows: bipolar disorder: 153 (95% CI = 26 to 902, p < .001); major depressive disorder: 2.7 (95% CI = 1.2 to 6.0, p = .013); any anxiety disorder: 6.7 (95% CI = 2.3 to 20, p < .001); any eating disorder: 2.4 (95% CI = 0.36 to 17, p = .36); and any substance use disorder: 3.3 (95% CI = 1.1 to 10, p = .040). CONCLUSIONS There is substantial lifetime psychiatric comorbidity in individuals with fibromyalgia. These results have important clinical and theoretical implications, including the possibility that fibromyalgia might share underlying pathophysiologic links with some psychiatric disorders.