The role of the nuclear receptor TLX in hippocampal neurogenesis and cognition has just begun to be explored. In this study, we generated a mouse model that expresses TLX under the control of a neural precursor marker nestin. Transgenic TLX expression led to enlarged brains with bigger hippocampal dentate gyrus and increased numbers of newborn neurons. Specific expression of TLX in adult hippocampal dentate gyrus, a brain region that is important for learning and memory, increased the numbers of proliferating neural progenitors and newborn neurons. Furthermore, the neural precursor-specific expression of the TLX transgene substantially rescued the neurogenic defects of mice with a deletion of the TLX gene. Consistent with increased neurogenesis in the hippocampus, the TLX transgenic mice exhibited enhanced cognition with increased learning and memory. These results suggest significant contributions of TLX to hippocampal neurogenesis, learning, and memory.