Research Ethics Committees (RECs) can be defined as independent bodies composed of people with various fields of expertise, includingmedical and scientific but not only those, who are responsible for ensuring that the biomedical research projects involving human subjects conform to the principles of biomedical research. The RECs are an ethical guarantee to protect the safety, integrity and rights involved in the experimentations and to avoid the recurrence of scientific and economic abuse. They are also a legal guarantee because their reviewing activities are acknowledged in national and international rules and regulations. Clinical trials in Nanotechnologymay represent a challenge for RECs in so far they must verify that the chosen methodologies are the most adequate to the aims of the protocols, in a context, that of nanotechnologies, characterized by many unknown and uncertainties with regards to particle toxicity, and interaction with the human body. For this reason, the REC should verify the risk to be assessed in terms of probability, magnitude and duration and verify the identification in the protocol of all those elements thatmay influence the risk, a risk that within nanotechnology represent an element hard to be identified. The role of RECs within NanotechnologyÂs clinical trials may be, then, decisive in the formulation of more specific operating procedures in this field.