Because the piglet is frequently used as a model for developmental disorders of the medullary serotonergic (5-HT) system in the human infant, this review compares the topography and developmental profile of selected 5-HT markers between humans in the first year of life and piglets in the first 60 days of life. The distribution of tryptophan hydroxylase-immunoreactive 5-HT neurons in the human infant medulla is very similar, but not identical, to that in the piglet. One notable difference is the presence of compact clusters of 5-HT neurons at the ventral surface of the piglet medulla. While it lacks these distinctive clusters, the human infant medulla contains potentially homologous 5-HT neurons scattered along the ventral surface embedded in the arcuate nucleus. Each species shows evidence of age-related changes in the 5-HT system, but the changes are different in nature; in the human infant, statistically significant age-related changes are observed in the proportional distribution of medullary 5-HT cells, while in the piglet, statistically significant age-related changes are observed in the levels of 5-HT receptor binding in certain medullary nuclei. Analyses of 5-HT receptor binding profiles in selected nuclei in the two species suggest that the equivalent postnatal ages for 5-HT development in piglets and human infants are, respectively, 4 days and 1 month, 12 days and 4 months, 30 days and 6 months, and 60 days and 12 months. Collectively, when certain species differences are considered, these data support the use of the piglet as a model for the human infant medullary 5-HT system.