There is mounting scientific evidence showing the importance of innate biological rhythms on disease onset and progression. Perhaps the most important of these is the circadian rhythm, a cycle of oscillations lasting approximately 24h. Recent work has shown that circadian rhythms are intrinsically linked to the immune system in a bidirectional fashion, and that disruption of these cycles can contribute to changes in pathology and quality of life (including fatigue, mood, and disability). This is particularly true in diseases of the nervous and immune systems. We review here the current preclinical and clinical literature to highlight interactions between circadian rhythms and multiple sclerosis, as well as its animal model, experimental autoimmune encephalomyelitis. We highlight potential benefits of chronotherapy (the temporal administration of immunomodulatory drugs) in an effort to increase treatment efficacy and reduce the negative side-effects of the drugs that often burden those suffering from the disease.