The ookinete is one of the most important stages of Plasmodium development in the mosquito. It is morphologically and biochemically distinct from the earlier sexual stages - gametocytes and zygote, and from the later stages - oocyst and sporozoites. Development to ookinete allows the parasite to escape from the tightly packed blood bolus, to cross the sturdy peritrophic matrix (PM), to be protected from the digestive environment of the midgut lumen, and to invade the gut epithelium. The success of each of these activities may depend on the degree of the biochemical and physical barriers in the mosquito (such as density of blood bolus, thickness of peritrophic matrix, proteolytic activities in the gut lumen etc.) and the ability of the ookinete to overcome these barriers. Ookinete motility, secretion of chitinase, resistance to the digestive enzymes, and recognition/invasion of the midgut epithelium all may play crucial roles in the transformation to oocyst. The overall sporogonic development of Plasmodium, therefore, depends on the results of the two-way manipulations between the parasite and the vector mosquito. Study of ookinete development and of the cellular and biochemical complexities of the mosquito gut may therefore lead to the design of novel strategies to block the transmission of malaria. This article reviews the intricate interactions between the parasite and the mosquito midgut in the context of development and transmission of Plasmodium parasites.