The biology and the pathology of the stress-activated protein kinases (SAPKs; p38s and c-Jun-NH(2)-terminal kinases (JNKs)) are somewhat confusing. In some systems, these enzymes augment cell proliferation whereas in other cells they support growth arrest and tumor suppressing activity. Similarly, in some types of cancer SAPKs' activity is suppressed while in others SAPKs seem to be an essential part of the transformative machinery. Revealing the role of SAPKs in cancer is important for planning an appropriate therapeutic strategy. Here, I describe the data supporting the role of SAPKs as tumor suppressors in some systems and as pro-oncogenic in others. Possible resolutions for the paradox of stress kinases are also discussed.