Cell migration is crucial for intrathymic T-cell differentiation. Chemokines and extracellular matrix proteins per se induce thymocyte migration, and recent data suggest a combinatorial role for these molecules in this event. For example, thymocyte migration induced by fibronectin plus CXCL12/SDF1-alpha (stromal cell-derived factor1-alpha) is higher than that elicited by the chemokine alone. If such interactions are relevant in the thymus, abnormal expression of any of these ligands and/or their corresponding receptors will lead to defects in thymocyte migration. At least in the murine model of Chagas disease, this seems to be the case. Therefore a better knowledge of this complex biological circuitry will provide new clues for understanding thymus physiology and designing therapeutic strategies targeting developing T cells.