Lung cancer is among the most common malignancies globally, is frequently associated with a poor prognosis, and is the second leading cause of cancer-related mortality in both genders. Resistance to treatment, heterogeneity, and invasiveness make lung cancer one of the most challenging tumors to combat. Drug repurposing is considered an advantageous strategy for expediting and economizing drug discovery, as it involves rebranding an existing drug for a new therapeutic use. Since depression is a prevalent psychiatric illness among individuals diagnosed with lung cancer, various selective serotonin reuptake inhibitors (SSRIs) used for the treatment of depression were examined for their possible use in lung cancer treatment as repurposed drugs. Herein, we evaluated the efficacy of SSRIs, both alone and in combination with various anticancer agents, in the treatment of lung cancer along with their mechanisms of action. The innovative approach of repurposing SSRIs offers hope by simplifying the drug discovery process and potentially revealing new therapeutic options for lung cancer. Exploring SSRIs' effects on lung cancer treatment may unlock unexpected avenues for combating this aggressive disease.