Prenatal and early neonatal immune development feature a series of novel maturational events that lack exact equivalents in later life. These events not only generate the diverse range of functional and regulatory immune cells needed to address postnatal disease challenges, but also help to determine the specific repertoire of host defenses as well as the balance of postnatal immune responses. Additionally, the immune system provides homeoregulatory oversight of tissues and organs helping to maintain appropriate function in later life. This occurs via prenatally generated myelomonocytic cells that seed virtually every organ and tissue of the body. Because these early life immune maturational events are timed to critical windows of development and are also interlinked with other nonimmune system processes, disruption of a novel early life immune maturational event can result in childhood and adult immune dysfunction and increased health risk. Impaired immune maturation can be of various forms including changes in postnatal host defense, altered immune surveillance, a propensity for autoreactivity, or susceptibility to allergic hypersensitivity disease (e.g., asthma).