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Many pediatric diseases are linked to underlying immune dysfunction that produces problematic responses to common infectious challenges and other conditions. During childhood, immune dysfunction manifests as: 1) increased susceptibility to certain infections, 2) misregulated inflammation with tissue damage, fatigue and secondary infections, 3) autoimmune disease and 4) allergic conditions. Both environmental and genetic risk factors contribute to a variety of pediatric immune-related illnesses. Ironically, the environmental risk factors are usually considered as one large continuum of equivalent chemical, physical and emotional factors spanning the entirety of a child’s development. But the reality is that some prenatal and neonatal environmental factors are most likely to cause the underlying pediatric immune dysfunction necessary for inflammatory, autoimmune and allergic disease. In contrast, other childhood environmentalfactors are usually triggers that activate or challenge the dysfunctional immune system leading directly to disease. Exposure to these triggers represents a final step in the overall disease process. Knowledge of both the causative agents for immune dysfunction as well as the triggering factors is important. However, viewing these prenatal and childhood factors as one continuum of risk is not always helpful. These distinct groups of environmental factors need to be recognized separately if prevention of immune dysfunction and management of immune-based diseases are to be optimized. This mini-review provides a unifying hypothesis concerning causative environmental factors vs triggering events for several important pediatric diseases. Improved recognition of these different steps should help pediatricians to better address these diseases.