To date, five distinct groups of mitogen activated protein kinases (MAPKs) have been characterized in mammals: extracellular signal-regulated kinases (ERKs) 1 and 2 (ERK1/2), c-Jun amino-terminal kinases (JNKs) 1, 2, and 3, p38 isoforms α, β, γ, and δ , ERKs 3 and 4, and ERK5; all sharing the enzyme commission number EC 2.7.11.24. MAPKs can be activated by a wide variety of different stimuli, but in general, ERK1 and ERK2 are preferentially activated in response to growth factors and phorbol esters, while the JNK and p38 kinases are more responsive to stress stimuli ranging from osmotic shock and ionizing radiation to cytokine stimulation. Although each MAPK has unique characteristics, a number of features are shared by the MAPK pathways studied to date. Each family of MAPKs is composed of a set of three sequentially acting kinases: a MAPK, a MAPK kinase (MAPKK or MAP2K), and a MAPKK kinase (MAPKKK or MAP3K). p38 (also known as CSBP, mHOG1, RK, and SAPK2) is the archetypal member of the second MAPK-related pathway in mammalian cells. The p38 module consists of several MAPKKKs, including MEKKs 1-4, MLK2 and -3, DLK, ASK1, Tpl2 (a.k.a. Cot), and Tak1, the MAPKKs MEK3 and MEK6 (a.k.a. MKK3 and MKK6, resp.), and the four known p38 isoforms (α, β, γ, and δ). In mammalian cells, the p38 isoforms are strongly activated by environmental stresses and inflammatory cytokines but not appreciably by mitogenic stimuli. Most stimuli that activate p38 also activate JNK, but only p38 is inhibited by the anti-inflammatory drug SB203580 (Axon 1363 and Axon 1465 (HCl salt; water soluble), which has been extremely useful in delineating the function of p38.