Apolipoprotein E (apoE) is a multifunctional glycosylated protein characterized by its wide tissue distribution. Despite its importance in lipid transport and atherosclerosis pathogenesis, apoE is associated with neurodegenerative disorders such as Alzheimer's disease (AD) and Parkinson disease, and autoimmune disorders such as multiple sclerosis and psoriasis. Among others, the role of apoE in modulating inflammation and oxidation is crucial in elucidating the risk factors of the above diseases since the function of apoE is closely linked with both proinflammatory and antiinflammatory cytokines. Moreover, apoE modulates inflammatory and immune responses in an isoform-dependent manner. Correspondingly, inflammatory cytokines can either upregulate or downregulate the production of apoE in various tissue types. However, studies on the interactions between apoE and cytokines occasionally yield conflicting results, highlighting the complex roles of apoE and cytokines in various disorders. The present paper summarizes the current knowledge about the cross-talk between apoE and cytokines, with emphasis on the effects of apoE on the Th1/Th2 balance.