This study examines problem behavior over time in 59 boys with fragile X syndrome (FXS), aged 4–12 years, using the Child Behavior Checklist (CBCL). Approximately 49% of the boys scored within the borderline or clinical range on total problem behavior, while 56–57% scored in the borderline or clinical range on the attention and thought problems subscales, and 26% scored in this range on the social problems subscale. With a mean of 2.5 assessments per child, behavior problems were stable during the 3-year period of study. Total problem behavior was higher for children who displayed autistic behavior, were rated as low in adaptability, had mothers with higher maternal education levels, and were on medication. Mothers with more education also rated their children as having more attention, thought, and total problems. Children taking medication differed from boys who were not taking medication on social problems, but not on attention and thought problems. Low adaptability and more autistic characteristics predicted thought problems. © 2002 Wiley-Liss, Inc.