Tourette's disorder (TD) is a neuropsychiatric disorder that onsets in childhood and appears to result from an interaction of genetic and environmental factors. The goal of the current prospective longitudinal study is to examine the onset of TD in offspring of parents with TD. At-risk children and control children were enrolled between the ages of 3 and 6 years and prospectively studied with yearly structured assessments over intervals of 2–5 years. Of 34 at-risk children free of tics at baseline, 10 (29%) subsequently developed a tic disorder, including 3 with TD. None of the 13 control children developed a tic disorder (P = 0.045). OCD or subclinical OCD emerged in 11 cases but no controls (P = 0.021). Finally, ADHD occurred in 14 at-risk children but no controls (P = 0.005). When at-risk families were dichotomized into bilineal or unilineal categories, rates of TD in children with two affected parents were three times the rate observed for children with one affected parent. These findings support the hypothesis that at least some cases of TD result from a complex genetic etiology. TD, OCD, and ADHD are significantly increased in children with TD parents. Furthermore, the risk is even greater when both parents are affected. Finally, our diagnosis of tic disorders in 21% of subjects initially reported by parents to be unaffected affirms the value of structured clinical assessments. © 2003 Wiley-Liss, Inc.