In secretory organs, such as the liver, the pancreas, and the adipose tissue, endoplasmic reticulum (ER) stress plays a key role in the etiology of cell disturbances implicated in many diseases. Although much less studied, ER stress also is present in skeletal muscle. In the present review, we hypothesize that ER stress may have important metabolic consequences in skeletal muscle. This review presents the situations in which ER stress is activated in skeletal muscle and its metabolic consequences.