The assembly of neural circuits is dependent upon the generation of specific neuronal subtypes, each subtype displaying unique properties that direct the formation of selective connections with appropriate target cells. Actions of transcription factors in neural progenitors and postmitotic cells are key regulators in this process. LIM-homeodomain transcription factors control crucial aspects of neuronal differentiation, including subtype identity and axon guidance. Nonetheless, their regulation during development is poorly understood and the identity of the downstream molecular effectors of their activity remains largely unknown. Here, we demonstrate that theLhx2transcription factor is dynamically regulated in distinct pools of thalamic neurons during the development of thalamocortical connectivity in mice. Indeed, overexpression ofLhx2provokes defective thalamocortical axon guidancein vivo, while specific conditional deletion ofLhx2in the thalamus produces topographic defects that alter projections from the medial geniculate nucleus and from the caudal ventrobasal nucleus in particular. Moreover, we demonstrate thatLhx2influences axon guidance and the topographical sorting of axons by regulating the expression of Robo1 and Robo2 guidance receptors, which are essential for these axons to establish correct connections in the cerebral cortex. Finally, augmenting Robo1 function restores normal axon guidance in Lhx2-overexpressing neurons. By regulating axon guidance receptors, such as Robo1 and Robo2, Lhx2 differentially regulates the axon guidance program of distinct populations of thalamic neurons, thus enabling the establishment of specific neural connections.