This study examined quantitative magnetic resonance volumes of the thalamus and hippocampus and determined their relationship with cognitive function and clinical seizure characteristics in a sample of 46 unilateral temporal lobe epilepsy (TLE) subjects (20 left and 26 right) and 29 controls. The hippocampus and thalamus exhibited different patterns of volume abnormality, different associations with clinical seizure characteristics, and different patterns of relationship with cognitive measures. Hippocampal volume reduction was primarily ipsilateral to the seizure focus, and thalamic volume reduction was bilateral. Ipsilateral hippocampal volume was significantly correlated with both early neurodevelopmental features (age of seizure onset) and disease characteristics (duration of epilepsy), whereas thalamus integrity was related only to disease variables. Hippocampal volume showed a selective association with verbal memory performance. In contrast, both left and right thalamic volumes were significantly correlated with performance on both memory and nonmemory cognitive domains. These findings underscore the importance of thalamic atrophy in chronic TLE and its potential implications for cognition.