Background: This study examined the predictors, mediators and moderators of parent stress in families of preschool-aged children with developmental disability. Method: One hundred and five mothers of preschool-aged children with developmental disability completed assessment measures addressing the key variables. Results: Analyses demonstrated that the difficulty parents experienced in completing specific care- giving tasks, behaviour problems during these care-giving tasks, and level of child disability, respectively, were significant predictors of level of parent stress. In addition, parents' cognitive appraisal of care-giving responsibilities had a mediating effect on the relationship between the childs level of disability and parent stress. Mother's level of social support had a moderating effect on the relationship between key independent variables and level of parent stress. Conclusions: Difficulty of care-giving tasks, difficult child behaviour during care-giving tasks, and level of child disability are the primary factors which contribute to parent stress. Implications of these findings for future research and clinical practice are outlined.