Cytokines are proteins produced by leukocytes and other cells that function as intercellular mediators acting on several target tissues, resulting in multiple biologic actions. Over the last decade, medical research has explored the interaction between cytokines and sleep disorders. The aim of this review is to illustrate recent advances in knowledge about the relationship between cytokines and disorders of excessive sleepiness. Cytokines may have an important role in mediating excessive daytime sleepiness in sleep loss or insomnia. Alterations of the immune system have also been associated with narcolepsy. The relationship between cytokines and hormonal regulatory mechanisms may explain symptoms like fatigue and sleepiness in chronic inflammatory diseases. Cytokines may play an important role in the pathogenesis of obstructive sleep apnea and cardiovascular consequences of this condition. New biologic treatments targeting cytokines have been investigated in conditions characterized by sleep disturbance.