Objectives: The aims and objectives of this systematic review are to inves-tigate the different theories underlining major depression and suicide while exploring the correlation between BDNF, major depression and suicide. Method: Literature was researched through the University of Malta research platform and statistical reports published by the Maltese National Statistics Office, Eurostat and World Health Organisation were consulted. Depression: Low blood BDNF levels have been identified to occur in major depression which normalise during remission. Additionally, since BDNF is associated with increased neural plasticity and survival and decreased at-rophy, exposure to chronic stress was identified to decrease BDNF levels and reverse such traits in laboratory rats. Single nucleotide polymorphism Val66Met on the BDNF gene has been identified to be responsible for de-creased activity-dependent secretion of BDNF and resultantly increased depressive features. Sertraline administration in human subjects and la-boratory rats has been also identified to have a neurogenic effect on sero-tonergic and BDNF neurons; increasing their expression. Suicide: Despite that suicide is commonly associated as part of the symptomatology of psychiatric disorders, in light that children of suicide attempters are six times more susceptible to attempt suicide than children of non-suicide at-tempters; recent research considered suicide as an independent phenomenon with a high percentage of heritability. Higher concentrations of chol-ecystokinin receptors and cholecystokinin B receptors have been reported in individuals who died by suicide. Conclusion: Large randomised replicated research looking into BDNF, major depression and suicide is still absent. Further research is necessary to validate the reported findings.