Malaria, caused by protozoan parasites of the genus Plasmodium continues to be a major global health burden, with an estimated 450,000 deaths annually and half of the world’s population at risk of infection. There is still no reliable vaccine available and resistance against frontline anti-malaria drugs is emerging. Thus, new drugs and intervention strategies are urgently needed, in order to fight the parasite and get closer to the goal of malaria eradication. The sexual gametocyte stages, which are taken up from the blood by Anopheles mosquitoes, are of special interest in this context. Being the only developmental stage of the parasite that is transmissible between human and mosquito hosts, they provide a prime target for new transmission-blocking intervention strategies. However, despite their high relevance for such strategies, the molecular mechanisms driving the switch from asexual replication to sexual development of malaria parasites remain poorly understood.