Sepsis is one of the leading causes of mortality and morbidity among neonates worldwide and especially affects the preterm neonates in resource-restricted settings. The infection may be acquired in utero, from the mother's genital tract or postnatally from the community or hospital environment and personnel. Factors including the time of exposure, size of the inoculum, immunity in the host, and virulence of the infectious agent affect the severity and course of illness. Culture-independent diagnostics, sepsis prediction scores, antibiotic stewardship, and preventive strategies including hand hygiene are ongoing efforts for reducing the neonatal sepsis burden.