Seawater desalination using nuclear energy is an inevitable option for the production of potable water. It is a reliable and economical way to alleviate global concerns on climate change and water scarcity issues. However, producing potable water from a co-located nuclear power plant raises some concerns regarding pathways of contamination of radioactivity to the final water. This paper examines all possible contamination pathways and analyses the preventive measures that are used both in design and operation of nuclear desalination plants. Innovative measures such as the use of heat pipes are also presented. Experience with the commissioned systems and practices related to the quality of the product water for 250 demonstrated reactor-years, shows no examples of contamination.