Nanomaterials have different chemical, physical and biological characteristics than larger materials of the same chemical composition. These differences give nanotechnology a double identity: their use implies novel and interesting medical and/or industrial applications but also potential danger for human and environmental health. Here, we briefly review the most important types of nanomaterials, the difficulties in assessing safety or toxicity, and describe existing test protocols used in nanomaterial safety evaluation. In general, the big challenge of nanotechnology, particularly for nanomedicine (nano-bioengineering), is to understand which nano-specific characteristics interact with particular biological systems and functions in order to optimize the therapeutic potential and reduce the undesired responses. The evaluation of the safety of medicinal nanomaterials, especially for long-term application, is an important challenge for the near future. At present, it is still too early to predict, on the basis of the characteristics of the nanomaterial, a possible biological response because no reliable database exists. Therefore, a case-by-case approach for hazard identification is still required, so it is difficult to establish a risk assessment framework.