Malaria remains one of the most prevalent tropical and infectious diseases in the world, with an estimated more than 200 million clinical cases every year. In recent years, the mosquito stages of the parasite life cycle have received renewed attention with some progress being made in the development of transmission-blocking strategies. From gametocytes to late ookinetes, some attractive antigenic targets have been found and tested in order to develop a transmission blocking vaccine, and drugs are being currently screened for gametocytocidal activity, and also some new and less conventional approaches are drawing increased attention, such as genetically modified and fungus-infected mosquitoes that become refractory to Plasmodium infection. In this review some of those strategies focusing on the progress made so far will be summarized, but also, the challenges that come from the translation of early promising benchwork resulting in successful applications in the field. To do this, the available literature will be screened and all the pieces of the puzzle must be combined: from molecular biology to epidemiologic and clinical data.