All over the world, people with sickle cell disease (an inherited condition) have premature deaths and preventable severe chronic complications, which considerably affect their quality of life, career progression, and financial status. In addition, these people are often affected by stigmatisation or structural racism, which can contribute to stress and poor mental health. Inequalities affecting people with sickle cell disease are also reflected in the distribution of the disease—mainly in sub-Saharan Africa, India, and the Caribbean—whereas interventions, clinical trials, and funding are mostly available in North America, Europe, and the Middle East. Although some of these characteristics also affect people with other genetic diseases, the fate of people with sickle cell disease seems to be particularly unfair. Simple, effective interventions to reduce the mortality and morbidity associated with sickle cell disease are available. The main obstacle preventing better outcomes in this condition, which is a neglected disease, is associated with inequalities impacting the patient populations. The aim of this Commission is to highlight the problems associated with sickle cell disease and to identify achievable goals to improve outcomes both in the short and long term.