The mitogen-activated protein (MAP) kinase family consists of extracellular signal-regulated protein kinase (ERK), p38 kinase, and c-Jun N-terminal kinase (JNK) and transduces signals from the extracellular environment to the cytoplasm and nucleus. MAP kinase signaling involves a multistep kinase cascade including MAP kinase kinase kinase (MAPKKK), MAP kinase kinase (MAPKK), and MAP kinase. The MAP kinase subtypes are constitutively expressed in articular chondrocytes and they regulate chondrocyte function, including differentiation, apoptosis, inflammatory responses, and activation of matrix metalloproteinases. Therefore, imbalance or destruction of homeostasis regulating MAP kinase activity is related to the pathogenesis of cartilage diseases such as osteoarthritis. This chapter describes methods for measuring and modulating MAP kinase subtype activity in primary cultured articular chondrocytes and cartilage explants.