Phosphoinositide 3-kinases (PI3Ks) catalyse the synthesis of specific members of the family of lipids collectively known as 'phosphoinositides'. These PI3Ks products can in turn modulate activation of many downstream proteins, ultimately regulating several cellular processes. Mammalian cells possess eight PI3Ks which are grouped into three classes based on their structure and substrate specificity. While class I and III PI3Ks have been extensively investigated, our understanding of the three class II members has only improved in most recent years. This chapter will summarise some of the available information on mammalian class II PI3Ks and their physiological roles.