Sickle cell disease is a blood disorder, and means the part of the red blood cell that carries oxygen from the lungs to the body tissues (haemoglobin) is abnormal. It is a genetic disorder and occurs when people inherit abnormal genes from both parents. It is more common in people originating from tropical Africa, and the Caribbean, Mediterranean, Indian, and Middle Eastern regions. Some types of sickle cell disease cause more severe symptoms than others, but in general people with the disease may be tired and weak (due to anaemia), and have severe and recurrent pain in the bones (referred to as crises), have more infections, more problems with breathing, and more chance of having a stroke. Sickle cell disease contributes to the death of children in the first five years of life, and infants aged six to 12 months are particularly at risk. Malaria infection is known to trigger a sickle cell crisis. So preventing malaria in people with sickle cell disease may also help to reduce crises and all the problems that go along with it. Health professionals often recommend life-long drugs to prevent malaria infections (chemoprophylaxis) for people with sickle cell disease living in these high risk areas for malaria. However, it is important to assess how effective this may be and what the adverse effects there might be from taking these drugs over a long period of time. This review of trials identified two small trials involving 223 people with homozygous sickle cell disease (commonly called sickle cell anaemia). These showed benefit in terms of reducing the number of sickle cell crises, blood transfusions, hospital admissions, and increasing the mean haemoglobin levels, but they did not collect data on potential adverse effects. More research is needed, therefore, to be sure of the benefits and to assess possible problems of drug resistance, and other potential long-term adverse effects that may be associated with continuous treatment.