Malnutrition, secondary to deficiency in uptake of proteins, metal elements or vitamins, consistently results in changes in the thymus gland. The organ undergoes a severe atrophy due to apoptosis-induced thymocyte depletion, particularly affecting the immature CD4 þ CD8 þ cells, as well as a decrease in cell proliferation. Such a feature is apparently linked to a hormonal imbalance, involving decrease of leptin and consequent raise of glucocorticoid hormone levels in the serum. Interestingly, this picture can be reversed after appropriate diet rehabilitation. The thymic microenvironment is also affected in malnutrition: morphological changes in thymic epithelial cells were found, together with a decrease of thymic hormone production by these cells. Additionally, intrathymic contents of extracellular proteins, such as fibronectin, laminin and collagens, are increased in the thymuses from malnourished children. Conjointly, the bulk of data discussed herein clearly points to the notion that the thymus gland is a target in malnutrition. Nevertheless, further relevant information regarding the physiology of the thymus, including the cytokine=chemokine secretion as well as the positive and negative selection events driven by TCR=MHC-peptide interactions in malnutrition, remains to be defined. These are questions that need to be answered in order to have a better understanding of the immunodeficiency seen in malnourished individuals.