Mortality is markedly elevated in hemodialysis (HD) patients. Between 30 and 50% of prevalent patients have elevated serum levels of inflammatory markers such as C-reactive protein and IL-6. The presence of inflammation, chronic or episodic, has been found to be associated with increased mortality risk. The causes of inflammation are multifactorial and include patient-related factors, such as underlying disease, comorbidity, oxidative stress, infections, obesity, and genetic or immunologic factors, or on the other side, HD-related factors, mainly depending on the membrane biocompatibility and dialysate quality. The adequate knowledge of these causes and their prevention or treatment if possible may contribute to improving the inflammatory state of patients who are on HD and possibly their mortality.