Objective: It has been reported in the literature that patients treated with hemodialysis (HD) suffer from various types of pain. The aim of this study was to summarize all the available evidence on pain in HD patients by conducting a new primary research among HD patients and using the method of systematic literature review. Methods: Primary research included 194 patients treated at HD units in the Split-Dalmatia County Croatia. P ysicians filled out a questionnaire about patients’ HD procedure and comorbidities. Patients filled out a questionnaire consisting of validated individual questionnaires that were already translated and used in Croatian language: visual-analogue pain scale, Edmonton symptom assessment system, Satisfaction with life scale, Short form with 36 health items and Charlson comorbidity index, as well as data about sociodemographics. Three systematic reviews on pain in hemodialysis patients were conducted: a scoping systematic review about pain in HD patients, a systematic review about risk factors associated with pain in HD patients and a third systematic review about epidemiology and intensity of pain in HD patients. The bibliographic databases of MEDLINE, Scopus, PsycINFO and CINAHL were systematically searched using complex and extensive search strategy. Studies in all languages were taken into account. The data from the included studies were extracted and a descriptive analysis was performed. Quality of included studies was analyzed with STROBE checklist and Cochrane's risk of bias assessment tool. Results: Primary research has shown that 49% of patients treated with HD suffered from the current pain, 16% complained of acute pain, and chronic pain was reported by 56% of respondents. The percentage of intense pain was 91%, 81% and 83% respectively. Different results for different types of pain were determined by examining the correlation between the various factors that have been described in the literature as potentially related to HD pain. Considering that this was a cross-sectional research, it was difficult to make inferences about the cause-and-effect relationship. The scoping systematic review of the literature included 158 studies, which were categorized into epidemiological studies, studies on specific pain syndromes and eventually qualitative and interventional studies on pain in HD patients. A total of 67 studies involving 7,818 participants (median number of participants = 60) were included in the systematic overview of the numerous risk factors associated with pain in HD patients in very heterogeneous populations and environments. Most of the studies reported on common risk factors such as age, sex, body mass index, race and/or ethnicity, marital status, total duration of HD treatment, various comorbidities and biochemical parameters. Other studies have presented specific factors such as type, regimen, phase or place of HD, type of HD membrane, type, dose or administration site of erythropoiesis stimulating agent (ESA). Studies have shown that these factors can contribute to an increase in the occurrence of general pain and also encourage the appearance of different types, sites and causes of pain in HD patients (eg generalized pain, arterial access pain, headache, osteomuscular pain, etc.). Third systematic review analyzed a total of 52 studies with 6,917 participants. The prevalence of acute and chronic pain in HD patients was 82% and 92% respectively. Significant number of patients suffered from intense pain. Various sites and causes of pain were described, with most studies portraying generalized pain, pain associated with arteriovenous (AV) vascular access, headache and osteomuscular pain. The current structure of evidence has shown significant deficiencies, and the results showed a marked inconsistency. Most od the available studies were observational, involving small sample of respondents and using inadequate statistical data processing methods as well as an non-validated scales of pain intensity estimation. Conclusion: A significant proportion of patients treated with HD suffer from suboptimally treated, high intensity pain which has a significant negative impact on daily functioning. Pain in the HD population should be recognized as an important public health problem, and it is necessary to constantly promote timely detection and treatment as a clinical and research priority in terms of reducing disability and improving the quality of everyday life.