Memories that have strong emotions associated with them are particularly resilient to forgetting. This is not necessarily problematic, however some aspects of memory can be. In particular, the involuntary expression of those memories, e.g. intrusive memories after trauma, are core to certain psychological disorders. Since the beginning of this century, research using animal models shows that it is possible to change the underlying memory, for example by interfering with its consolidation or reconsolidation. While the idea of targeting maladaptive memories is promising for the treatment of stress and anxiety disorders, a direct application of the procedures used in non-human animals to humans in clinical settings is not straightforward. In translational research, more attention needs to be paid to specifying what aspect of memory (i) can be modified and (ii) should be modified. This requires a clear conceptualization of what aspect of memory is being targeted, and how different memory expressions may map onto clinical symptoms. Furthermore, memory processes are dynamic, so procedural details concerning timing are crucial when implementing a treatment and when assessing its effectiveness. To target emotional memory in its full complexity, including its malleability, science cannot rely on a single method, species or paradigm. Rather, a constructive dialogue is needed between multiple levels of research, all the way 'from mice to mental health'.This article is part of a discussion meeting issue 'Of mice and mental health: facilitating dialogue between basic and clinical neuroscientists'.We are grateful to the Royal Society for their support of the costs of attending this meeting ‘Of mice and mental health: facilitating dialogue between basic and clinical neuroscientists' convened by Amy L. Milton and Emily A. Holmes. R.M.V. is supported by the European Union's Horizon 2020 research and innovation programme under grant agreement no. 705641 (SUAI/023/RG92025). A.L.-Z. was supported by a Cambridge International Scholarship awarded by the Cambridge Commonwealth, European and International Trust. R.N.H. is supported by the UK Medical Research Council Programme (SUAI/010/ RG91365). E.A.H. receives support from the Karolinska Institutet and the Lupina Foundation. Funding to pay the Open Access publication charges for this article was provided by the UK Medical Research Council (SUAI/013/ RG91365).