Problem: Sickle cell disease is an inherited, chronic hematological disorder, which under certain conditions changes the red blood cells to sickle-shaped cells due to an abnormality in the hemoglobin. It is associated with profound complications that affect different organ systems. Due to the complex nature of this disease, sickle cell disease significantly affects children’s overall health. This, in fact, suggests the need to assess all health domains in order to improve the health related quality of life for children with sickle cell disease. The aim of this review is to identify strategies that help to improve health- related quality of life of children with sickle cell disease. Methodological approach: A literature review was conducted using multimodal search strategy of multiple databases that include CINAHL, Medline, PubMed, Science Direct, Psych Info, SCOPUS, and Web of Science. This review covers the period between 1995 and 2015. Finding and Conclusion: Sixteen articles were retrieved. The literature suggested that educational and cognitive behavior therapy interventions improved various aspects of health. This review found that both interventions were helpful in improving the participants’ knowledge about the disease and increasing their ability to manage their disease symptoms, thus improving the physical, mental and cognitive aspects of health.