Cytokines are involved both in the immune response and in controlling various events in the central nervous system, that is, they are equally immunoregulators and modulators of neural functions and neuronal survival. On the other hand, cytokine production is under the tonic control of the peripheral and the central nervous system and the cytokine balance can be modulated by the action of neurotransmitters released from nonsynaptic varicosities [131]. The neuroimmune interactions are therefore bidirectional-cytokines and other products of the immune cells can modulate the action, differentiation, and survival of neuronal cells, while the neurotransmitter and neuropeptide release play a pivotal role in influencing the immune response. Cytokines and their receptors are constitutively expressed by and act on neurons in the central nervous system, in both its normal and its pathological state, but cytokine overexpression in the brain is an important factor in the pathogenesis of neurotoxic and neurodegenerative disorders. Accordingly, it can be accepted that the peripheral and central cytokine compartments appear to be integrated, and their effects might synergize or inhibit each other; however, it should always be taken into account that they are spatiotemporally differentially regulated. New concepts are reviewed in the regulation of relations between cytokine balance and neurodegeneration, including intracellular receptor-receptor, cell-cell, and systemic neuroimmune interactions that promote the further elucidation of the complexities and cascade of the possible interactions between cytokines and the central nervous system.