Within the past five years genome-scale gene essentiality data sets have been published for ten diverse bacterial species. These data are a rich source of information about cellular networks that we are only beginning to explore. The analysis of these data, very heterogeneous in nature, is a challenging task. Even the definition of 'essential genes' in various genome-scale studies varies from genes 'absolutely required for survival' to those 'strongly contributing to fitness' and robust competitive growth. A comparative analysis of gene essentiality across multiple organisms based on projection of experimentally observed essential genes to functional roles in a collection of metabolic pathways and subsystems is emerging as a powerful tool of systems biology.