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ABSTRACT Purpose: Whereas ethical considerations on imaging techniques and interpretations of neuroimaging results flourish, there is not much work on their preconditions. In this paper, therefore, we discuss epistemological considerations on neuroimaging and their implications for neuroethics. Results: Neuroimaging uses indirect methods to generate data about surrogate parameters for mental processes, and there are many determinants influencing the results, including current hypotheses and the state of knowledge. This leads to an interdependence between hypotheses and data. Additionally, different levels of description are involved, especially when experiments are designed to answer questions pertaining to broad concepts like the self, empathy or moral intentions. Interdisciplinary theoretical frameworks are needed to integrate findings from the life sciences and the humanities and to translate between them. While these epistemological issues are not specific for neuroimaging, there are some reasons why they are of special importance in this context: Due to their inferential proximity, ‘neuro-images’ seem to be self-evident, suggesting directness of observation and objectivity. This has to be critically discussed to prevent overinterpretation. Additionally, there is a high level of attention to neuroimaging, leading to a high frequency of presentation of neuroimaging data and making the critical examination of their epistemological properties even more pressing. Conclusions: Epistemological considerations are an important prerequisite for neuroethics. The presentation and communication of the results of neuroimaging studies, the potential generation of new phenomena and new ‘dysfunctions’ through neuroimaging, and the influence on central concepts at the foundations of ethics will be important future topics for this discipline.