Protein kinases are the key components of almost every signalling pathway involved in normal development and disease. MAPKs play a key role in the regulation of diverse cellular programs and participate extensively in the control of cell fate decisions such as proliferation, differentiation, and death, as well as in the regulation of stress responses. The main stress-activated MAPKs are the p38 and c-Jun N-terminal kinase (JNK) families. The p38MAPK family has four isoforms encoded by distinct genes located tandemly in 2 chromosomes: p38, , and . Although the role of all p38s have been thought to be similar, we think the less-studied members p38 and have different and specific regulation and function. We will discuss about our recent findings that suggest that these kinases have specific function and regulation. We will focus our attention in their implication in obesity related diseases.