Past research has shown that children with autism and their families have compromised quality of life (QOL) in several domains. This study examined QOL and parental concerns in children with autism during early childhood, childhood, and adolescence compared to children with Attention Deficit Disorder/Attention Deficit Hyperactivity Disorder (ADD/ADHD) and to typical controls from a US national sample. Families with children diagnosed with autism reported more profound QOL effects than families of children with ADD/ADHD or unaffected controls. Children with autism were significantly less likely to attend religious services, more likely to miss school, and less likely to participate in organized activities. Parental concerns over learning difficulty, being bullied, stress-coping, and achievement were overwhelming in the autism group relative to the comparison groups.