Artemisinin combination therapy (ACT) is recommended by the World Health Organization (WHO) as first line treatment for uncomplicated malaria both in adults and children. During pregnancy, ACT is considered safe only in the second and third trimester, since animal studies have demonstrated that artemisinin derivatives can cause foetal death and congenital malformation within a narrow time window in early embryogenesis. During this period, artemisinin derivatives induce defective embryonic erythropoiesis and vasculogenesis/angiogenesis in experimental models. However, clinical data on the safety profile of ACT in pregnant women have not shown an increased risk of miscarriage, stillbirth, or congenital malformation, nor low birth weight, associated with exposure to artemisinins in the first trimester. Although further studies are needed, the evidence collected up to now is prompting the WHO towards a change in the guidelines for the treatment of uncomplicated malaria, allowing the use of ACT also in the first trimester of pregnancy.