Currently, we have a poor understanding of why some food allergies are outgrown and others are not. Deciphering the immune basis of the natural resolution of food allergy will likely provide critical information for developing new therapies for the treatment of persistent food allergies. There are limited cohort studies that have followed children with food allergy over time, but information generated from such cohorts points to features of innate and adaptive immunity, as well as environmental differences (microbiome) that discriminate those with persistent versus transient food allergy. Studies from mouse models highlight the importance of novel subsets of memory B cells rather than plasma cells combined with antigen re-exposure and T-cell help in the maintenance of IgE. In this review we discuss these findings from human cohorts and experimental systems and discuss existing gaps in our knowledge.