Phosphoinositol-3-kinases (PI3 Kinases, PI3K) are a family of lipid kinases that mediate many intracellular signaling responses in both physiological and pathophysiological states. PI3 Kinase is a heteroduplex with three classes (I, II, & III) of catalytic domain. The class 1 PI3 Kinases are made up of a p85 regulatory protein and a p110 catalytic domain. There are 4 isoforms of the class 1 p110 catalytic domains. Class 1(A) include a, b, g and class 1(B) d. They are activated downstream via receptor tyrosine kinases or G-protein coupled receptors. Once activated, PI3Ks generate phosphatidylinositol 3,4,5-trisphosphate (PIP3) from PIP2. It was later found that PTEN, a lipid phosphatase, acts opposite to PI3K by dephosphorylating PIP3, converting it to PIP2, thus deactivating the effects of PI3K. Increased levels of PIP3 in the cell leads to the activation of many key signaling regulators including Akt and PDK as well as calcium release. One of the primary roles of PI3K is its regulation of cell growth and cell metabolism. Both of these play a critical role in cancer as some believe that a tumor’s shift to glycolysis is due to the activation of PI3K. PI 3-kinases have been linked with numerous disease states, including cancer, diabetes, allergic response, hypertension, cardiac contractility, atherosclerosis, sepsis and autoimmune/ inflammatory disorders.