Despite abundant knowledge on the neural basis of memory functions in the human brain, stimulus-specific memory traces- engrams-have long remained elusive. In this article, recent developments that start to shed light on the mechanisms underlying the formation, modification and potential degradation of engrams are reviewed. Stimulus-specific memory representations appear to occur at different levels of brain organization, from spike rates of individual cells via time-frequency signatures of small-scale neural networks to distributed activity patterns. However, memories undergo transformation whenever they are recalled. Thus, novel methodological approaches need to be employed in order to identify considerably modified engrams. Furthermore, engrams are impaired in a number of diseases involving memory dysfunction. This article is concluded with a description of recent translational work on altered content-specific memory representations in the context of Alzheimer’s disease.