Most organisms have a circadian clock that coordinates gene expression to the rhythm of a 24-hour cycle. Researchers led by Erol Fikrig at Yale University now report that expression of a gene required for detecting pathogenic viruses and bacteria also ebbs and flows under clock control, hitting a minimum during sleeping hours and a maximum during wakeful periods. This direct molecular link between circadian clocks and innate immune systems could help medical researchers know when a patient is most vulnerable to infection and when to administer a vaccine for optimal protection against a pathogen (Immunity, DOI: 10.1016/j.immuni.2011.12.017). Fikrig and coworkers focused on expression of a gene called Toll-like receptor 9 (TLR9), which is a component of the mammalian innate immune system that acts as a first scout for invading microbes. They found that mice had a better chance of survival against pathogens when an infection happened during the animal’s wakeful hours, when TLR9 was maximally expressed. The team also found that vaccines provided better long-term protection against pathogens when the vaccine had been given during wakeful times of the day.