During each cycle of asexual endomitotic division in erythrocytes, the malaria parasite makes a fundamental and crucial decision: to continue to invade and proliferate or to differentiate into gametocytes ready for continuation of sexual development. The proteins and regulatory pathways involved in Plasmodium sexual development have been of great interest in recent years as targets for blocking malaria transmission. However, the 'Holy Grail', the master switch orchestrating asexual-to-sexual commitment and further differentiation, has remained elusive - until now. Here we highlight the recent studies identifying the epigenetic and transcriptional master regulators of sexual commitment and discuss the key players in reversible phosphorylation pathways involved in sexual and zygote differentiation.