A review of the recent data on the biological mechanisms of depression, including the мonoamine hypothesis, the diathesis-stress model and the chronobiological model, is presented. These and other biological hypotheses are viewed in the aspect of the current genetic, neurochemical and neuroimaging studies as well as in relation to different treatment approaches. Depression seems not to be a homogenous disease and may be caused by different factors. Genetic factors and stressful life events play an important role in the young age. Chronic stress, chronobiological disturbances and comorbid somatic disease are relevant to middle-aged and elderly people. Moreover, recurrent and chronic depression are accompanied by cognitive impairment, social dysfunction and neurodegeneration. All these factors should be taken into consideration in the development of personalized complex treatment programs.