Caregivers of persons with Autism Spectrum Disorders (ASD) are prone to depression and psychological problems, which have an impact on their children's challenging behaviors. Positive cognitions include specific positive thinking patterns that enhance one's ability to effectively manage daily activities and promote mental health. The purpose of this research is to test the mediating effects of positive cognitions on the relationship between caregivers' depression and their children's challenging behaviors among 117 caregivers of persons with ASD. Positive cognitions were found to have mediating effects on the relationship between caregiver's depression and their children's challenging behaviors in this sample of caregivers of persons with ASD. Nurses are in a strategic position to include in their interventions those strategies that strengthen positive cognitions in order to improve the caregivers' positive cognitions and well-being, which, in turn will have an impact on their children's challenging behaviors.