End stage renal disease patients need to undergo hemodialysis lifelong to prolong their survival. Fatigue is the commonest and multifactorial problem among patients on hemodialysis. There are many factors leading to physical and mental fatigue among patients on hemodialysis which has a detrimental effect on their day-to-day activities and health related quality of life. This critical review is aimed at exploring the prevalence, the associating factors, and the impact of fatigue on health-related quality of life of patients undergoing hemodialysis. Online databases such as PubMed index, Web of science, PsycINFO, CINAHL, Google Scholar, etc., were scrutinised to get the full text articles. The prevalence of fatigue is high among patients on hemodialysis and estimated to be between 41% to 83.8%. Existing studies have listed out the several factors associated with fatigue into different aspects such as Physiological factors, Psychological factors, Social factors, Dialysis/ Disease related factors, Changes in Biochemical Parameters. Ageing, comorbidities, feminine gender, poor sleep quality are the common associating factors of fatigue. Depression and anxiety are also more frequently associated with fatigue. High prevalence of fatigue impairs the daily activities of the patients and leading to decreased working capacity, restricted functioning, mood instability, sleep disturbances, impaired family and social functioning. These consequences decrease the healthrelated quality of life and increases the morbidity and mortality of the patients on hemodialysis. Therefore, this critical review helps to expand the knowledge of the health care professionals to assess, identify and intervene the fatigue as early as possible.