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Physical activity, by definition, is any skeletal muscle body movement that results in energy expenditure. In the last few decades, a plethora of scientific evidences have accumulated and confirmed the beneficial role of physical activity as a modifiable risk factor for a wide variety of chronic diseases including cardiovascular diseases (CVDs), diabetes mellitus and cancer, among others. Autoimmune diseases are a heterogeneous group of chronic diseases, which occur secondary to loss of self-antigen tolerance. With the advent of biological therapies, better outcomes have recently been noted in the management of autoimmune diseases. Nonetheless, recent research highlights the salient role of modifiable behaviors such as physical inactivity on various aspects of the immune system and autoimmune diseases. Physical activity leads to a significant elevation in T-regulatory cells, decreased immunoglobulin secretion and produces a shift in the Th1/Th2 balance to a decreased Th1 cell production. Moreover, physical activity has been proven to promote the release of IL-6 from muscles. IL-6 released from muscles functions as a myokine and has been shown to induce an anti-inflammatory response through IL-10 secretion and IL-1β inhibition. Physical activity has been shown to be safe in most of autoimmune diseases including systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), multiple sclerosis (MS), inflammatory bowel diseases (IBD), as well as others. Additionally, the incidence of RA, MS, IBD and psoriasis has been found to be higher in patients less engaged in physical activity. As a general trend, patients with autoimmune diseases tend to be less physically active as compared to the general population. Physically active RA patients were found to have a milder disease course, better cardiovascular disease (CVD) profile, and improved joint mobility. Physical activity decreases fatigue, enhances mood, cognitive abilities and mobility in patients with MS. In SLE patients, enhanced quality of life and better CVD profile were documented in more physically active patients. Physically active patients with type 1 diabetes mellitus have a decreased risk of autonomic neuropathy and CVD. Both fibromyalgia and systemic sclerosis patients report decreased disease severity, pain, as well as better quality of life with more physical activity. Further, SSc patients improve their grip strength, finger stretching and mouth opening with increased level of exercise. The purpose of this paper is to review the clinical evidence regarding the safety, barriers to engagement, and impact of physical activity on autoimmune diseases. [ABSTRACT FROM AUTHOR]