Surgery for craniofacial resections is continuously improving, enabling the extirpation of tumors once considered unresectable. Nevertheless, the physical and psychological sequelae of these procedures and their affect on patients' everyday lives have not been systematically evaluated. The purpose of this study was to estimate the impact of anterior skull base surgery on the long-term quality of life (QOL) and on the family relations of patients with anterior skull base tumors. Demographic, medical and outcome data on 69 patients undergoing subcranial surgery for extirpation of tumors were retrospectively analyzed. Within this group, 35 patients and their lay caregiver successfully completed a disease-specific questionnaire. We did not find significant differences in QOL estimation between patients and their caregivers. Malignancy had the most significant impact on QOL, leading to a significant decrease in the overall score. Radiotherapy significantly decreased the scores in the specific symptoms and influence upon emotions domains. Age and comorbidity reduced the scores in the role of performance and physical function domains. A better correlation was found between the scores of married couples than between patients and lay caregivers who weren't married. Eighty three percent of the married couple's replies noted that the disease and surgery did not influence their relations. We conclude that malignancy, radiotherapy, comorbidity and age over 60, significantly impair quality of life in patients undergoing anterior skull base surgery. We suggest that a rehabilitation program should be implemented in these patients in order to improve their overall QOL.