Inflammatory mediators play a significant role in the pathophysiology of major depressive disorder (MDD) and bipolar disorder (BD). Both disorders are characterized by distinct immune profiles, which are crucial for differential diagnosis and personalized treatment strategies. The review highlights that MDD is associated with increased levels of pro-inflammatory cytokines such as IL-6 and TNF-α, while BD shows greater involvement of chemokines and markers of innate immunity. Additionally, BD is linked to dynamic changes in T cells, with differentiation defects in childhood that normalize in adulthood. MDD is also associated with signs of immune senescence, including increased levels of IL-4 and IL-10. CRP levels are elevated in both MDD and BD, with higher levels observed in BD patients. CRP levels fluctuate with the phases of the illness, with higher levels during manic episodes and lower levels after remission. Blood count ratios such as NLR, PLR, and MLR are also elevated in BD compared to MDD, suggesting a greater activation of the immune system in BD. Cytokines and chemokines, including IL-6, TNF-α, IL-10, IL-4, CCL2, and IL-8, show distinct patterns between MDD and BD. BD is associated with higher levels of certain chemokines, such as CCL3 and CCL11, and IL-8, indicating a greater involvement in cell trafficking. Monocyte gene expression and T cell populations also differ between MDD and BD. BD patients show increased expression of inflammatory genes and higher levels of Th17 cells, while MDD patients exhibit reduced levels of T regulatory cells. These differences suggest that the immune system is more activated in BD, contributing to the pathophysiology of the disorder. The review emphasizes the importance of understanding these immune differences to develop targeted treatments for MDD and BD. The findings suggest that immune markers could be useful in differentiating between the two disorders and in guiding personalized treatment approaches. However, the heterogeneity of the disorders and the influence of various factors such as childhood trauma and pharmacological treatments complicate the interpretation of immune markers. Despite these challenges, the role of immune dysregulation in mood disorders is increasingly recognized, and further research is needed to fully understand the mechanisms and develop effective interventions.Inflammatory mediators play a significant role in the pathophysiology of major depressive disorder (MDD) and bipolar disorder (BD). Both disorders are characterized by distinct immune profiles, which are crucial for differential diagnosis and personalized treatment strategies. The review highlights that MDD is associated with increased levels of pro-inflammatory cytokines such as IL-6 and TNF-α, while BD shows greater involvement of chemokines and markers of innate immunity. Additionally, BD is linked to dynamic changes in T cells, with differentiation defects in childhood that normalize in adulthood. MDD is also associated with signs of immune senescence, including increased levels of IL-4 and IL-10. CRP levels are elevated in both MDD and BD, with higher levels observed in BD patients. CRP levels fluctuate with the phases of the illness, with higher levels during manic episodes and lower levels after remission. Blood count ratios such as NLR, PLR, and MLR are also elevated in BD compared to MDD, suggesting a greater activation of the immune system in BD. Cytokines and chemokines, including IL-6, TNF-α, IL-10, IL-4, CCL2, and IL-8, show distinct patterns between MDD and BD. BD is associated with higher levels of certain chemokines, such as CCL3 and CCL11, and IL-8, indicating a greater involvement in cell trafficking. Monocyte gene expression and T cell populations also differ between MDD and BD. BD patients show increased expression of inflammatory genes and higher levels of Th17 cells, while MDD patients exhibit reduced levels of T regulatory cells. These differences suggest that the immune system is more activated in BD, contributing to the pathophysiology of the disorder. The review emphasizes the importance of understanding these immune differences to develop targeted treatments for MDD and BD. The findings suggest that immune markers could be useful in differentiating between the two disorders and in guiding personalized treatment approaches. However, the heterogeneity of the disorders and the influence of various factors such as childhood trauma and pharmacological treatments complicate the interpretation of immune markers. Despite these challenges, the role of immune dysregulation in mood disorders is increasingly recognized, and further research is needed to fully understand the mechanisms and develop effective interventions.