Sixty years ago, Haldane proposed that certain abnormalities in red blood cells could be selected as malaria-resistance genes. Population studies have confirmed that many human polymorphisms confer resistance to severe malaria, although the mechanisms of protection remain unknown. A recent article proposes a new mechanism for explaining the protective effects of hemoglobin C (HbC). HbC-containing red blood cells have modified displays of malaria surface proteins that reduce parasite adhesiveness and could reduce the risk of severe disease.