The major aim of the current study is to understand health related quality of life (HRQoL) domains from children’s own perspective. Specifically, we aim to determine the HRQoL in childhood chronic illnesses and to compare scores with healthy children. A cross-sectional study design with a total of 149 chronically ill children and 162 healthy participants was consecutively enrolled in this study. The Arabic-PedsQL^TM-Version 0.4 Scales were used to assess HRQoL in both groups. Results showed that the chronically ill children reported more problems with physical, emotional and school functioning (all significant at p < 0.001) when compared to their healthy peers. This significant difference extended to all HRQoL domains except social functioning. Children with chronic renal failure, diabetes mellitus and sbina bifida showed the lowest HRQoL scores among the group in all domains. The impact of chronic diseases on children’s HRQoL is significantly evident in Jordan. Therefore, a holistic and individual approach to the health care and education in those children requests reintegration programmes that are best facilitated by coordinated efforts between child's home, school and hospital.