One principal aim of research in the signal transduction field is to identify targets for therapeutic intervention, in an attempt to modify disease and curtail human suffering. Diseases such as chronic inflammation, atherosclerosis, diabetes and cancer exact a huge toll on health, in physical, social and financial terms. Defective signaling mechanisms are central to their pathogenesis. One candidate signaling molecule that is presently undergoing intense investigation is the c-Jun N-terminal kinase. With roles described in almost all classes of disease, the main questions are what type of inhibitor to use and when exactly to use it during the disease course?