The phosphoinositide 3-kinase (PI3K)/Akt/mTOR pathway is implicated in the pathogenesis of lymphoma. Deeper understanding of the diversity and biological impact of this pathway has led to the development of specific inhibitors to this pathway. Preclinical data in cell lines, patient samples and disease models have broadened our understanding of PI3K inhibition. Several PI3K inhibitors are currently in advanced stages of clinical development. Idelalisib is the first agent of this new substance class to be approved in chronic lymphocytic leukemia and follicular lymphoma. Other agents specifically target different PI3K isoforms and show promising clinical efficacy.