Due to their exciting properties, engineered nanoparticles have obtained substantial attention over the last two decades. As many types of nanoparticles are already used for technical and biomedical applications, the chances that cells in the brain will encounter nanoparticles have strongly increased. To test for potential consequences of an exposure of brain cells to engineered nanoparticles, cell culture models for different types of neural cells are frequently used. In this review article we will discuss experimental strategies and important controls that should be used to investigate the physicochemical properties of nanoparticles for the cell incubation conditions applied as well as for studies on the biocompatibility and the cellular uptake of nanoparticles in neural cells. The main focus of this article will be the interaction of cultured neural cells with iron oxide nanoparticles, but similar considerations are important for studying the consequences of an exposure of other types of cultured cells with other types of nanoparticles. Our article aims to improve the understanding of the special technical challenges of working with nanoparticles on cultured neural cells, to identify potential artifacts and to prevent misinterpretation of data on the potential adverse or beneficial consequences of a treatment of cultured cells with nanoparticles.