The phosphoinositide 3-kinase (PI3K)/AKT pathway plays an important role in cancer development and progression. Mammalian target of rapamycin (mTOR) is a downstream effector of this pathway and is responsible for various cellular functions including mRNA translation, cell cycle progression and cellular proliferation. Activation of the PI3K/AKT pathway plays an important role in normal and neoplastic T and B cell proliferation. Abnormal activation of this pathway is seen in various hematologic malignancies. This knowledge has lead to an interest in evaluating the use of mTOR inhibitors in hematologic malignancies. The prototype mTOR inhibitor is rapamycin. Three other drugs are being evaluated in clinical trials. This review focuses on the biologic function of the PI3K/AKT/mTOR pathway and the mTOR inhibitors that are in clinical development for treatment of hematological malignancies.