The Plasmodium ookinete is the developmental stage of the malaria parasite that invades the mosquito midgut. The ookinete faces two physical barriers in the midgut which it must traverse to become an oocyst: the chitin- and protein-containing peritrophic matrix; and the midgut epithelial cell. This chapter will consider basic aspects of ookinete biology, molecules known to be involved in midgut invasion, and cellular processes of the ookinete that facilitate parasite invasion. Detailed knowledge of these mechanisms may be exploitable in the future towards developing novel strategies of blocking malaria transmission.