Abstract
Protein coding genes exhibit different degrees of intolerance to loss-of-function variation. The most intolerant genes, whose function is essential for cell or/and organism survival, inform on fundamental biological processes related to cell proliferation and organism development and provide a window on the molecular mechanisms of human disease. Here we present a brief overview of the resources and knowledge gathered around gene essentiality, from cancer cell lines to model organisms to human development. We outline the implications of using different sources of evidence and definitions to determine which genes are essential and highlight how information on the essentiality status of a gene can inform novel disease gene discovery and therapeutic target identification.