Mood disorders (MD) are important and frequent psychiatric illness. The management of patients affected by these conditions represents an important factor of disability as well as a significant social and economic burden. The "in-vivo" studies can help researchers to understand the first developmental events of the pathology and to identify the molecular and non-molecular targets of therapies. However, they have strong limitations due to the fact that human brain circuitry can not be reproduced in animal models. In addition, these neural pathways are difficult to be selectively studied with the modern imaging (such as Magnetic Resonance and Positron Emitted Tomography/Computed Tomography) and non-imaging (such as electroencephalography, magnetoencephalography, transcranial magnetic stimulation and evoked potentials) methods. In comparison with other methods, the "in-vivo" imaging investigations have higher temporal and spatial resolution compared to the "in-vivo" non-imaging techniques. All these factors make difficult to fully understand the aetiology and pathophysiology of these disorders, and consequently hinder the analysis of the effects of pharmacological and non-pharmacological therapies, which have been demonstrated effective in clinical settings. In this review, we will focus our attention on the current state of the art of imaging in the assessment of treatment efficacy in MD. We will analyse briefly the actual classification of MD; then we will focus on the "in vivo" imaging methods used in research and clinical activity, the current knowledge about the neural models at the base of MD. Finally the last part of the review will focus on the analysis of the main markers of response to treatment.