Osteoarthritis ( OA ), the most common type of osteoarthrosis, is a leading cause of disability in the elderly. Although a number of studies have shown that predispositions include aging, obesity, joint injury, congenital anomalies, joint deformities etc., but the exact etiology and pathogenesis are not fully understood and there is currently no effective disease-modifying treatment. Under the comprehensive effects of systemic and local factors, changes in the structure and metabolism of the articular cartilage occur progressively, culminating in articular cartilage softening, ulceration, local stripping and joint edge of the bone and cartilage excrescence formation etc. The initiation and progression of OA subtypes is a complex process that at the molecular level probably involves many cell types and signaling pathways. Increasing evidence implicates that the endoplasmic reticulum stress ( ERS ) and c-Jun N-terminal kinase ( JNK ) signaling pathway are probably involved to some degree in OA etiology and pathogenesis. Endoplasmic reticulum is an important organelle in cells, which is easy to cause the endoplasmic reticulum stress, leading to the endoplasmic reticulum related death, while the apoptosis of chondrocytes is one of the important pathological manifestations of osteoarthritis. C-Jun N-terminal kinase signal pathway was discovered in the past 20 years which was related to the cell differentiation, apoptosis, stress response and a variety of diseases occurrence and development. This review summarized the current knowledge of ERS as well as the JNK signaling pathway and their interactions regulating OA progression.