A food-induced anaphylactic reaction can occur within seconds to a few hours following exposure to the causal food allergen and often affects multiple organ systems including gastrointestinal, cutaneous, respiratory, and cardiovascular. A conundrum in the allergy field is that consumption of the same allergen can cause reactions of vastly different severity in separate individuals; one patient may experience a mild non-life-threatening reaction characterized by pruritis of lips or urticaria whereas another may experience a life-threatening reaction that involves respiratory and cardiovascular compromise leading to loss of consciousness and sometimes death. While there are tests available to determine the predictive risk value of a positive food challenge test or clinical reactivity, there is currently no reliable method to distinguish between individuals who are at risk of mild non-life-threatening versus life-threatening reaction. Recent research has significantly advanced our understanding of the involvement of immune pathways in the effector phase of food-induced anaphylaxis; a void remains regarding our understanding of the contribution of these pathways to severity of disease. In this review, we discuss mild non-life-threatening versus life-threatening food-induced anaphylaxis and factors (co-morbidities and immune activation) that predispose individuals to more severe disease. Furthermore, we summarize recent advancements in our understanding of the involvement of underlying immune pathways in systemic and food-induced anaphylaxis in mouse systems and discuss how these pathways may contribute to more severe disease phenotype.