In mammals, endoplasmic reticulum (ER) stress, oxidative stress, and inflammatory responses compose the major defense networks that help the cells adapt to and survive stress conditions caused by biochemical, physiological and pathological stimuli. However, chronic ER stress, oxidative stress, or inflammation have been found to be associated with the initiation and progression of a variety of human diseases in the modern world. Under many pathophysiologic conditions, ER stress response, oxidative stress, and inflammatory responses are integrated and amplified in specialized cell types to facilitate the progression of disease. In the past few decades, ER stress response, oxidative stress, and inflammation as well as their interactive relationships have been hot research topics in biomedicine. In this review, we summarize the recent advance in our understanding of the cross talk between ER stress response, oxidative stress, and inflammation in immunity and in inflammatory and metabolic diseases.