Major depressive disorder (MDD) is one of the most prevalent mental illness and a leading cause of disability worldwide. Despite a range of effective treatments, more than 30% of patients do not achieve remission as a result of conventional therapy. In these circumstances the identification of novel drug targets and pathogenic factors becomes essential for selecting more efficacious and personalized treatment. Increasing evidence has implicated the role of inflammation in the pathophysiology of depression, revealing potential new pathways and treatment options. Moreover, convergent evidence indicates that MDD is related to disturbed neurogenesis and suggests a possible role of neurotrophic factors in recovery of function in patients. Although the influence of antidepressants on inflammatory cytokines balance was widely reported in various studies, the exact correlation between drugs used and specific cytokines and neurotrophins serum levels often remains inconsistent. Available data suggest anti-inflammatory properties of selective serotonin reuptake inhibitors (SSRIs), selective serotonin and noradrenaline inhibitors (SNRIs), and tricyclic antidepressants (TCAs) as a possible additional mechanism of reduction of depressive symptoms.