In October 2020, the Keystone Symposia Global Health Series hosted a Keystone eSymposia entitled 'Tissue Plasticity: Preservation and Alteration of Cellular Identity'. The event synthesized groundbreaking research from unusually diverse fields of study, presented in various formats, including live and virtual talks, panel discussions and interactive e-poster sessions. The meeting focused on cell identity changes and plasticity in multiple tissues, species and developmental contexts, both in homeostasis and during injury. Here, we review the key themes of the meeting: (1) cell-extrinsic drivers of plasticity; (2) epigenomic regulation of cell plasticity; and (3) conservedmechanisms governing plasticity. A salient take-home conclusion was that there may be conservedmechanisms used by cells to execute plasticity,with autodegradative activity (autophagy and lysosomes) playing a crucial initial step in diverse organs and organisms.