Regulation of T- and B-lymphocyte survival and death is crucial for maintaining immune homeostasis. Unresponsiveness to death signals can result in lymphoproliferative disorders including cancer and autoimmunity, whereas lymphocytes hypersensitive to such signals can be manifested as immunodeficiencies. Often within these cells, cytokines and their receptors regulate the critical balance between life and death. It is becoming ever more apparent that within these effector cascades, Janus tyrosine kinases (Jak) and signal transducers and activators of transcription (Stat) act as key regulatory components. Invaluable knowledge about Jaks and Stats has arisen from mice made genetically deficient in these mqlecules, tumor models, and proteomics/genomics, which has begun to define their role in survival versus apoptosis. These findings have also suggested how Jaks and Stats might be manipulated for therapeutic intervention in lymphoid-derived diseases. This review seeks to focus on the role of Jak tyrosine kinases and Stat transcription factors in mediating the lymphocyte life cycle.