Phosphatidylinositol 3-kinases (PI3Ks) include members of a unique and conserved family of intracellular lipid kinases that phosphorylate the 3-hydroxyl group of phosphatidylinositols and phosphoinositides. The resultant activation of many intracellular signalling pathways regulates various biological functions such as cell metabolism, survival, growth, proliferation, polarity, and apoptosis. PI3Ks are classified into three types: class I, II, and III. Of them, class I PI3K is most widely studied and plays an important role in the development and progression of tumours. In this review, we describe PI3K family members and their functions, especially the subunits of class I PI3K, their alterations in cancers, as well as PI3K inhibitors and their clinical trial status in cancer-targeted therapy.