While vaccines have been tremendously successful in reducing the incidence of serious infectious diseases, newborns remain particularly vulnerable in the first few months of their life to life-threatening infections. A number of challenges exist to neonatal vaccination. However, recent advances in the understanding of neonatal immunology offers insights to overcome many of those challenges.High disease burden in early life and recent advances in understanding neonatal immunology have created a renewed interest in neonatal vaccination and adjuvants. Neonates (defined as children less than four weeks old) and young infants are less protected against life-threatening diseases due to lack of vaccines or late administration. For instance, developing a Flu vaccine that can be given to infants younger than 6 months of age would significantly reduce worldwide morbidity and mortality from the disease. Recent research indicates that neonatal vaccination may be an effective strategy for protecting against early life infections such as influenza, respiratory syncytial virus (RSV), and pertussis. Bacillus Calmette-Guerin (BCG), a live vaccine against tuberculosis, demonstrates that a single dose of vaccine administered at birth can in principle confer lifelong protection Effective neonatal vaccination would be ideal especially for less privileged infants, for whom birth is often the only contact with health care systems. Neonatal vaccination therefore has the potential to improve vaccine coverage and confer protection before initial exposure to vaccine-preventable viral and bacterial infections. Alternative, indirect strategies include vaccination of the pregnant mother and/or other family members so as to “cocoon” the neonate against exposure to pathogens (for example, expectant mothers in the US are recommended to receive the Tdap and inactivated influenza vaccines [