Unipolar major depressive disorder (MDD) and bipolar disorder (BD) are among the world’s leading causes of disability. This chapter highlights the importance of neuroimaging in understanding their neural mechanisms. Depression affects limbic-corticostriatopallidothalamic regions. Structurally, depressed subjects showed increased volume of lesions in white matter (WMH) and decreased gray matter in prefrontal-striatum, orbitofrontal, anterior cingulate cortices, and hippocampus. Functionally, depressed subjects showed abnormal activation in amygdala and medial prefrontal cortex and dsyconnectivity in executive and emotional networks. BD was associated with frontocingulate, limbic-striatal, and hippocampus abnormalities. Specifically, BD subjects showed increased WMH in frontocortical and subcortical areas and altered microstructure in limbic-striatal, cingulate, thalamus, corpus callosum, and prefrontal regions. Functionally, abnormal activations in dorsolateral prefrontal and ventrolimbic regions, hypoconnectivity in the cinguloinsularopercular, mesoparalimbic, and cerebellar networks, and hyperconnectivity in affective and executive networks were also observed. These studies show congruence. Full integration of them would allow better understanding of mood disorders.