The article reviews the cognitive deficits associated with depression and their potential neurobiological underpinnings. Recent studies have reported both mnemonic deficits and executive impairments, particularly in set-shifting tasks, which occur independently of age, severity, subtype, task difficulty, motivation, and response bias. These deficits persist even after clinical recovery. The authors suggest that these deficits are not simple epiphenomena of depression but may be linked to interactions between motivation, affect, and cognitive function. They propose that understanding these interactions can provide insights into the interplay between dorsal and ventral prefrontal cortex in depression. The article also discusses the impact of depressive severity, subtype, and microvascular disease on cognitive performance, and the potential for persistent neuropsychological impairment upon recovery from depression. Finally, it highlights the importance of integrating neurocognitive and affective manifestations of depression into a functional neuroanatomical framework to better understand the pathogenesis of depressive disorders.The article reviews the cognitive deficits associated with depression and their potential neurobiological underpinnings. Recent studies have reported both mnemonic deficits and executive impairments, particularly in set-shifting tasks, which occur independently of age, severity, subtype, task difficulty, motivation, and response bias. These deficits persist even after clinical recovery. The authors suggest that these deficits are not simple epiphenomena of depression but may be linked to interactions between motivation, affect, and cognitive function. They propose that understanding these interactions can provide insights into the interplay between dorsal and ventral prefrontal cortex in depression. The article also discusses the impact of depressive severity, subtype, and microvascular disease on cognitive performance, and the potential for persistent neuropsychological impairment upon recovery from depression. Finally, it highlights the importance of integrating neurocognitive and affective manifestations of depression into a functional neuroanatomical framework to better understand the pathogenesis of depressive disorders.