Unpredictable chronic mild stress (UCMS) in rodents induces several changes in behavior and physiology that are similar to major depressive disorder (MDD) in humans. Although the specific brain areas, hormones, and genes that mediate this complex response to UCMS are important points for research and discussion, potential circadian mechanisms have also been considered for some time. Logan et al. (1) describe a compelling correlation between behavioral assays that are relevant to depression and the amplitude of daily locomotion and temperature rhythms in mice. Moreover, they correlate the amplitude of in vitro rhythms of circadian clock gene expression in the nucleus accumbens (NAc) and suprachiasmatic nucleus (SCN), the master circadian clock, with performance on the same tasks. These findings are relevant to two key aspects of MDD. First, MDD is often associated with disrupted circadian rhythms in behavior and physiology, and normalized rhythms often relate to an attenuation of symptoms. Second, MDD has been linked with decreased interest in normally rewarding activities, and the NAc is a key player in the processing of natural and drug-related rewards in rodents and humans (2). Logan et al. (1) describe UCMS-induced deficits on depression-related tasks that are correlated with rhythms of locomotion, core body temperature, and regionspecific clock gene expression. As a result, these findings could be an important step toward describing potential circadian mechanisms underlying MDD and depression-like responses to UCMS. Circadian rhythms in behavior and physiology are generated through the actions of endogenous clocks distributed throughout the brain and body. At the cellular level, these clocks use complex transcriptional-translational feedback loops that depend on the rhythmic expression of a wide array of clock genes (3). However, many researchers have focused on the highly rhythmic expression patterns of period circadian clock 1 or 2 genes (PER1 or PER2) as markers that track the function and phase of the more general circadian loop. Daily rhythms of clock gene expression in the SCN are generally thought to facilitate the clock functions of this brain area. Daily rhythms of PER1 and PER2 expression are also observed in many other brain areas outside of the SCN (4), areas known to be important in learning, memory, motivation, emotion, and reward-related processing. However, the importance of rhythms in clock gene expression per se is still unclear for most of these extra-SCN areas. To remain synchronized with environmental cycles, both SCN and extra-SCN rhythms are influenced by time cues, or zeitgebers. For example, the environmental light-dark cycle is a powerful zeitgeber that adjusts rhythms of period circadian clock gene expression in