© The Author 2016. The last 5 years have seen significant advances in our understanding of the molecular pathogenesis of B-cell lymphomas. This has led to the emergence of a large number of new therapeutic agents exploiting precise aspects of the tumor cells signaling pathways, surface antigens or microenvironment. The purpose of this comprehensive review is to provide a detailed analysis of the breakthrough agents in the field, with a focus on recent clinical data. We describe agents targeting the B-cell receptor pathway, Bcl-2 inhibitors, emerging epigenetic therapies, new monoclonal antibodies and antibody drug conjugates, selective inhibitors of nuclear export, agents targeting the programmed cell death axis and chimeric antigen receptor T cells.