The purpose of this study was to examine parental perceptions about Health Related Quality of Life (HRQoL) of typical education and special education students in Greece. The Pediatric Quality of Life Inventory (PedsQL) was administered to the parents of 251 children from typical schools, 46 students attending integration classes (IC) within a typical school and 97 students attending special education (segregated) schools. A two-way analysis of covariance indicated that, compared to their typically developing peers, children attending special education schools and IC were reported by their parents to have lower PedsQL scores. Compared to children attending special education schools, children attending IC showed no differences in all PedsQL domains but the emotional domain score (p < 0.05). Based on parents' responses, further improvements in special education settings and environments in the Greek educational system might be necessary to improve the HRQOL of students with disabilities.