Water treatment system and dialysis monitors are susceptible to microbial contaminations and periodical disinfection procedures are mandatory to obtain results requested from international standards and guidelines. Several chemical germicides or some physical treatments are on the market validated by device manufacturer according to medical device directives. With time, interfering substances from dialysis device or water are able to modify disinfection efficiency. Simulating-use testing is not a common procedure to validate disinfectants and recent data document as biofilm represents the most important cause of disinfection inefficacy. Some international standards include tests in the presence of various interfering substances but their use is not widespread. When using a disinfectant, residue toxicity, material compatibility and potential risks for the staff also have to be considered. A quality assurance program has to be implemented to obtain adequate performances and to improve results on patients.