This book provides current research on the regulation, function and role in health and disease of endoplasmic reticulum (ER) stress. The first chapter focuses on evidence that supports the role of endoplasmic reticulum stress, mitochondria-associated membranes (MAMs) microdomain and oxidative stress during obesity as a molecular pathway to type 2 diabetes mellitus (T2DM) development. Also, it addresses protein missfolding and mitochondria function as potential targets to improve metabolic derangements in obesity and T2DM. Chapter Two summarizes and discusses the current understanding of molecular mechanisms linking ER stress to beta cell fate. Chapter Three depicts the association between eIF2α kinase-linked pathways and diet-linked pathogenic responses (such as ones caused by microbes or nutritional abnormalities). Chapter Four reviews placental endoplasmic reticulum stress in the determination of pregnancy outcome. The last chapter discusses the role of ER stress in meditating the anticancer effects of tocotrienols.