Neonatal sepsis is one of the leading causes of neonatal mortality worldwide. Unlike in the adult population, there is a large variability in the clinical picture and therefore the difficulty to recognize and diagnose neonatal sepsis. In addition to this, there is a lack of clear diagnostic criteria that would aide clinicians in diagnosis and rapid treatment of sepsis. There has been much ongoing research in this area without any striking success. Neonatal sepsis can be divided into different categories based on the age of disease onset. Early onset neonatal sepsis occurs in the first 72 hours of the child’s life and is associated with various risk factors and physiological differences when compared to other age groups. The risk factors may be related to the mother, the child or the process of delivery. Early onset neonatal sepsis also has a specific set of pathogens that are most likely to cause disease. The two most common pathogens, E. coli and Group B streptococcus, have a tendency to exploit the neonates immature immune system resulting in possible complications. Several components of the neonates’ physiological inflammatory response have been researched for their value in diagnosis. The current evidence for C-reactive protein, procalcitonin, interleukin-6 and several other inflammatory reactants have shown variable results. The lack of a clear biomarker that would consistently confirm or exclude the diagnosis of neonatal sepsis continues to elude us. The continued exploration into the various markers and their combinations still needs to be researched so that a list of criteria can be developed in order to reduce the devastating results of the disease.