Immunologically, End Stage renal Disease (ESRD) is associated with some disorders in both innate and adaptive immune system in such a form that there is a coexistence of both immune activation and immune suppression. Although these disorders are complex yet thoroughly unknown, there is a close relation between the progressively defective immune system with side effects as well as mortality causes including cardiovascular problems, infections, and malignancies. From the other point, chronic inflammation as a major determinant of "dialysis syndrome" (including malnutrition, cachexia, and vasculopathy) is considered as the main factor of inability and mortality in dialysis patients. Such inflammation is generally arisen from immune system response to uremia and individual's repetitive contact with dialysis instruments and, in the long term, leads to premature aging via intensifying tissue degeneration. Therefore, the immune system is known as one of the most important therapeutic targets to reduce morbidity and mortality in uremic and dialysis patients. This review addresses different aspects as well as mechanisms of immune system dysfunction and possible therapeutics in dialysis patients.