While major advances in single cell transcriptomics have occurred, the epigenomics arena has only more recently gained momentum. Indeed, methods to track changes in different molecules present in biological samples have developed both in scale – providing a global view in each case – and in terms of resolution, allowing us today to disentangle heterogeneity within samples and access at the level of a single cell. The application of omics methods, comprising analysis of genomes, epigenomes, transcriptomes, proteomes and metabolomes, among other functional genomics techniques, individually or in combination, provides a wealth of valuable datasets. The treatment of these data with the development of artificial intelligence tools opens unprecedented avenues. The possibility to gain a holistic view of cells functioning within organs and during their formation will allow us to tackle fundamental questions of normal organism development and also to reveal early changes associated with disease onset and progression. In this editorial, we discuss the place of epigenomics research in an era where mapping cellular trajectories and mechanisms offers unique opportunities to address fundamental questions related to cell identity of key importance for medical applications.