A functional polymorphism in the promoter region of the 5-hidroxytryptamine transporter gene (5-HTTLPR), alters its transcription. Short allele (SS) variation decreases the transcriptional efficacy of serotonin, causing psychiatric disorders, major depressive disorder (MDD) and major depression in response to stressful life events. The aim of this study was to determine the current understanding of the role of 5-HTTLPR polymorphism in the development of depressive episodes and its response to treatment. Twenty-five articles were identified from PubMed, utilizing the following keyword, 5-HTT transporter gene, polymorphism, depression, stressful condition, psychiatric disorder. All articles were read and notes were made regarding study participant, measures, data analysis and results, and were used to write this review. The distribution of the SS allele in patients is associated with an increased risk of MDD following exposure to stressful events of life. Additionally, this genetic variant is closely associated with several psychiatric conditions such as suicidal behaviour, psychoses, personality disorders, and aggressive-impulsive traits.