Although a role for adult neurogenesis in specific forms of learning and in mediating some of the effects of antidepressants has received considerable attention in recent years, much less is known about how alterations in this unique form of plasticity may contribute to neurologic or psychiatric disorders. One way to begin to address this question is to link the functions of adult-born hippocampal neurons with specific endophenotypes of these disorders. Recent studies have implicated adult-born hippocampal neurons in pattern separation, a process by which similar experiences or events are transformed into discrete non-overlapping representations. Here, we propose that impaired pattern separation underlies the overgeneralization often seen in age-related memory impairments and in anxiety disorders and, therefore, represents an endophenotype for these disorders. We will present evidence that strategies aimed at stimulating hippocampal neurogenesis result in improved pattern separation. The development of novel pro-neurogenic compounds may therefore have therapeutic potential for patients who display pattern separation deficits.