Although glucose-6-phosphate dehydrogenase (G6PD) deficiency is less known in Western countries than in the Middle East and Africa, global migration and immigration are bringing ethnic groups with the highest incidence of this inherited genetic disorder into the US healthcare system. The G6PD enzyme is critical to protecting erythrocytes against oxidative stress, and deficiency may lead to hemolysis in the presence of certain environmental factors such as infection and some medications and foods. Neonatal jaundice, favism, and hemolysis are associated with exposure to increased oxidative stressors in patients with G6PD deficiency. By recognizing the potential for G6PD deficiency, clinicians can screen for the disorder and teach affected patients how to avoid triggers that result in harmful clinical manifestations.