Malaria parasites have evolved a complicated life cycle alternating between two hosts. Gametocytes are produced in the vertebrate hosts and are obligatory for natural transmission of the parasites through mosquito vectors. The mechanism of sexual development in Plasmodium has been the focus of extensive studies. In the postgenomic era, the advent of genome-wide analytical tools and genetic manipulation technology has enabled rapid advancement of our knowledge in this area. Patterns of gene expression during sexual development, molecular distinction of the two sexes, and mechanisms underlying subsequent formation of gametes and their fertilization have been progressively elucidated. However, the triggers and mechanism of sexual development remain largely unknown. This article provides an update of our understanding of the molecular and cellular events associated with the decision for commitment to sexual development and regulation of gene expression during gametocytogenesis. Insights into the molecular mechanisms of gametocyte development are essential for designing proper control strategies for interruption of malaria transmission and ultimate elimination.