In the wake of the development of insecticide resistance in mosquitoes, novel strategies for halting malaria transmission are being developed. These include the genetic modification (GM) of mosquitoes to become incompetent vectors. Although mosquito GM technologies are progressing rapidly, the rationale behind choosing anti-parasite molecules to be expressed by mosquitoes has received less attention. Here, questions are explored that that should be addressed during the strategic selection of these anti-Plasmodium molecules, focusing on antimicrobial peptides. Properties that will enhance the likelihood of success are discussed, and the need to plan an initial strategy to eliminate molecules that cause fitness costs to the mosquito is considered. Effector molecules with proven anti-sporogonic stage activity are reviewed, and the activity of a selection of these molecules is detailed. Copyright © 2010 Elsevier Ltd. All rights reserved.