The proto-oncogenic PI3K pathway is crucial for the integration of growth factor signaling and metabolic pathways to facilitate the coordination for cell growth. Since transformed cells have the ability to upregulate their anabolic pathways and selectively modulate a subset of metabolites functioning as anti- or pro-tumorigenic signal mediators, the question of how the levels of these metabolites are regulated has also become the center of attention for cancer researchers. Apart from its well-defined roles in glucose metabolism and peptide anabolism, the PI3K pathway appears to be a significant regulator of lipid metabolism and a potentiator of proto-oncogenic bioactive lipid metabolite signaling. In this review, we aim to describe the crosstalk between the PI3K pathway and bioactive lipid species of the three main lipid classes.