This issue presents a Focus of specially commissioned articles that discuss cell death in its multiple forms, implications for homeostatic physiology and disease and outstanding questions in this expanding field.

Proper development and homeostasis on the organismal scale fundamentally hinge on decisions between life and death on the cellular scale. When gone awry, cell death can lead to defects in development, cancer and immune disorders. The ongoing discovery of cell death types has led to a dizzying array of distinct forms to delineate. Key questions remain about the physiological relevance of cell death modes and the complex relationship between cell death and inflammation, with potential translational implications.

To showcase rapid advances in this field, we are delighted to publish our Focus on cell death. The Focus features commissioned articles written by leading experts on a range of topics, including the role of mitochondria in cell death, cell death types such as ferroptosis and pyroptosis, and cell death in cancer and immunity. The Focus is hosted on a dedicated page (https://www.nature.com/collections/fffdbefdba) and includes an online library of selected research articles, research highlights and commentary recently published in Nature Cell Biology.

A key question for studying any type of cell death is how cell death should be monitored, measured and analysed to enable proper data interpretation and robust conclusions. To that end, our online collection includes a Comment by Dixon and Lee in which they offer quick tips on the parameters that need to be carefully considered when designing experiments, acquiring data and drawing conclusions, including for example the effects of timing and cell proliferation, cell strains, cell culture methods and distinct cell death modalities.

Mitochondria are not only hubs for cellular metabolism but are also central to intrinsic apoptosis. Dewson, Tait and colleagues review the role of mitochondria in cell death and the complexity of BCL-2 family factors in regulating apoptosis. Increasing evidence suggests that distinct cell death mechanisms may not occur independently of each other and can engage the same cellular machineries and organelles for execution. The authors examine the function of mitochondria at the intersection of various cell death pathways, including intrinsic apoptosis and inflammatory cell death pathways such as necroptosis, pyroptosis and ferroptosis, and highlight emerging roles of non-lethal mitochondrial apoptotic signalling in cancer, immunity and ageing.

Cell death, inflammation and innate immunity are central to health and disease, but there is still much to learn about how dying cells, cell corpses and the signalling molecules they release are sensed by innate immune cells and contribute to adaptive immunity. Our Focus continues with a Review Article by Man and Kanneganti in which they provide an overview of how innate immune cells sense and respond to cell death signals and consider opportunities for effective therapeutics and disease treatment. They discuss inflammatory cell death pathways including PANoptosis, thought to share molecular and cellular features of pyroptosis, apoptosis and necroptosis.

Pyroptosis is a lytic form of cell death mediated by gasdermins, pore-forming proteins that disrupt membrane integrity. Chen and Broz review the conserved structures of gasdermins, mechanisms of pore-forming activation and how gasdermins can drive either pathological or protective immune responses, with implications for homeostasis and disease. They cover insights into the diverse functions of the gasdermin family, including in the context of non-lethal pore formation such as ion flux and unconventional secretion. Emerging research has shown that gasdermins can be activated without protease-mediated cleavage. In an Article in this issue, Chen, Wu and colleagues report cleavage-independent activation of intact gasdermin E to execute pyroptosis upon ultraviolet-C irradiation, discussed in a News & Views by Wu and colleagues.

Enormous progress has been made over the past decade to understand ferroptosis, an iron-dependent mode of necrotic cell death characterized by excessive lipid peroxidation. Yet questions remain about the complex function of iron in ferroptosis. A Perspective by Zhang in this issue focuses on the ‘ferro’ side of ferroptosis, including iron sources, iron regulation and dysregulation in disease. In their Review Article, Dai, Stockwell, Kroemer, Tang and colleagues offer a comprehensive overview of the core mechanisms of ferroptosis and the therapeutic opportunities and challenges they present. Nakamura and Conrad review the latest insights into ferroptosis and cancer, including ferroptosis involvement in cancer–immune cell crosstalk in the tumour microenvironment and approaches to manipulate the susceptibility of cancer cells to ferroptosis.

This issue also features research exploring ferroptosis. Key questions remain about the physiological role of ferroptosis, and in vivo imaging has been limited by the need for specific probes. Wood and colleagues performed three-colour live imaging of acute injury in the Drosophila embryo and showed that ferroptosis-like cell death can occur in vivo with a role in recruiting macrophages. The authors found evidence for a dual role for ferroptosis during inflammation. In the context of cancer, ferroptosis has been linked to tumour progression and could be a potential target for therapeutic intervention. An Article by Koeberle, Brabletz and colleagues shows that activation of the epithelial–mesenchymal transition can enhance ferroptosis susceptibility in cancer cells through Zeb1-mediated changes in phospholipid content. The authors demonstrate that this can be leveraged for potential therapeutic benefit in high-Zeb1-expressing cancer cell lines, highlighted in a News & Views by Winkelkotte and Schulze.

We are thrilled to present our Focus on cell death together with our online collection, which we hope will be enlightening and inspiring to our readers both new to and familiar with this evolving field. We extend our gratitude to the authors and referees for their contributions, and we look forward to Nature Cell Biology continuing to publish stimulating work to unravel and harness the biology of cell death.