Life flows over time, the fourth dimension of life, which shapes our days, months and years, and time is measured in the brain by ticking “clocks”. The suprachiasmatic nuclei (SCN) of the anterior hypothalamus, which function as a master biological clock, govern the sleep-wake cycle, as well as of endogenous rhythms in behavioral, hormonal and immune functions. Other neural cell groups act as “switches” of biological functions. For example, orexin-containing neurons in the dorsolateral hypothalamus play a key role in wake regulation and are involved in circuits underlying the transition from sleep to wake. Despite the wealth of knowledge accumulated in the last years on the regulation of the SCN and brain “switches”, the effect exerted by inflammatory signalling on these cell groups has been relatively neglected, though it can be implicated in diverse pathological and physiological conditions. Paradigmatic is, in this context, a severe neuroinflammatory condition represented by human African trypanosomiasis (HAT) or sleeping sickness. This neglected parasitic disease, which is fatal if untreated, is hallmarked by alterations of the sleep-wake cycle and sleep pattern, and experimental findings implicate neural-immune interactions in such dysregulation. Novel data indicate that brain timing changes have a translational value to monitor HAT severity. In the context of physiological conditions, a number of data in the last years have pointed out that normal aging is hallmarked by low-grade chronic inflammatory activity at the cellular and molecular levels. A puzzling aspect of aging is represented by the frequent dysregulation of the sleep/wake cycle, and data will be presented on aging-related changes of brain clock/s and on the response of the aging brain to inflammatory challenges . Neural-immune interactions which influence the brain timing machinery play thus a key role in health and disease.