The cell uses a complex signal transduction network both to respond to changes in its microenvironment and to integrate all of its intracellular signals. Actions of various signals in the cellular signal transduction network converge at the mitogen-activated protein kinase (MAPK) cascades, which lead to and activate transcription factors in the nucleus and other effectors throughout the cell. Extracellular signal-regulated kinases (ERKs), c-Jun N-terminal kinases/stress-activated protein kinases (JNK/SAPK), and p38 are some of the better characterized members of the MAPK family. Unlike ERK mainly responding to mitogens, JNK/SAPK was originally identified as a stress-related kinase and it has been extensively demonstrated to be associated with apoptosis. However, recent studies have further indicated that JNK/SAPK also has many functions other than the promotion of apoptosis. The repertoire of the JNK/SAPK pathway is wide-ranging, and its functions can vary, and even oppose each other, depending on the cell types and stimuli. It remains a challenge for biomedical scientists to elucidate the distinct role of JNK/SAPK in each model system.