Early onset sepsis (EOS) is a blood stream infection that occurs, by varying definitions, during a neonate’s first 3 or 7 days of life. In the United States, Streptococcus agalactiae and Escherichia coli are the most common pathogens associated with EOS. Worldwide, Klebsiella, Acinetobacter, and Staphylococcus aureus are also common etiologies. Early recognition of risk factors and clinical concerns for EOS facilitates timely treatment. Current research is focusing on ways to reduce unnecessary treatment of infants with risk factors for EOS without true infection, while still appropriately detecting and treating infants with EOS.