The endoplasmic reticulum (ER) regulates protein synthesis, folding and trafficking, cellular responses to stress, and intracellular calcium (Ca 2+ ) levels. Accumulation of misfolded proteins and alterations in Ca 2+ homeostasis in the ER cause ER stress. Eukaryotic cells possess at least three different mechanisms to adapt to ER stress and thereby survive : (1) transcriptional activation of genes encoding ER-resident chaperones, (2) translational attenuation which limits further accumulation of misfolded proteins, and (3) the ER-associated degradation (ERAD) pathway, which restores the folding capacity. If the cells are exposed to prolonged and/or strong ER stress, they are destroyed by apoptosis. Recent evidence has indicated that ER stress signaling pathways are mediated by several intracellular signaling pathways and play an important role in the pathogenesis of conformational diseases. The main purpose of this review is to summarize current knowledge about the ER stress signaling pathways and their involvement in the pathogenesis of diseases.