Bipolar disorder (BD) is a severe, chronic disease with a heritability of 60–80%. BD is frequently misdiagnosed due to phenomenological overlap with other psychopathologies, an important issue that calls for the identification of biological and psychological vulnerability and disease markers. Altered structural and functional connectivity, mainly between limbic and prefrontal brain areas, have been proposed to underlie emotional and motivational dysregulation in BD and might represent relevant vulnerability and disease markers. In the present laboratory review we discuss functional and structural neuroimaging findings on emotional and motivational dysregulation from our research group in BD patients and healthy individuals at risk to develop BD. As a main result of our studies, we observed altered orbitofrontal and limbic activity and reduced connectivity between dorsal prefrontal and limbic brain regions, as well as reduced integrity of fiber tracts connecting prefrontal and subcortical brain structures in BD patients and high-risk individuals. Our results provide novel insights into pathophysiological mechanisms of bipolar disorder. The current laboratory review provides a specific view of our group on altered brain connectivity and underlying psychological processes in bipolar disorder based on our own work, integrating relevant findings from others. Thereby we attempt to advance neuropsychobiological models of BD.