This paper reviews the role of anhedonia, a loss of pleasure or lack of reactivity to pleasurable stimuli, in depression and proposes a heuristic model to explain its pathophysiology. The model suggests that anhedonia arises from dysfunctional interactions between stress and brain reward systems. The review integrates three bodies of literature: (1) anhedonia as an endophenotype of depression, (2) dopamine's role in depression, and (3) the impact of stress on depression. Animal data indicate that stress negatively affects mesocorticolimbic dopaminergic pathways, which are crucial for incentive motivation and reinforcement learning. The paper also discusses the validity of anhedonia as an endophenotype, highlighting its heritability, state-independence, and familial association. Behavioral studies show that depressed individuals exhibit reduced affective responses to positive cues, impaired encoding and retrieval of positive information, and diminished ability to modulate behavior based on reinforcement. Neuroimaging studies reveal reduced activation in reward-related brain regions in depressed individuals. The role of dopamine in depression is explored through studies on DA metabolites, DA depletion, and molecular imaging, suggesting reduced DA transmission. The paper also reviews the role of stress in the development and exacerbation of depression, noting that chronic and uncontrollable stressors are particularly depressogenic. Finally, the effects of stress on dopaminergic pathways are discussed, with acute stressors activating mesocorticolimbic DA neurons and chronic stressors blunting DA release in these pathways.This paper reviews the role of anhedonia, a loss of pleasure or lack of reactivity to pleasurable stimuli, in depression and proposes a heuristic model to explain its pathophysiology. The model suggests that anhedonia arises from dysfunctional interactions between stress and brain reward systems. The review integrates three bodies of literature: (1) anhedonia as an endophenotype of depression, (2) dopamine's role in depression, and (3) the impact of stress on depression. Animal data indicate that stress negatively affects mesocorticolimbic dopaminergic pathways, which are crucial for incentive motivation and reinforcement learning. The paper also discusses the validity of anhedonia as an endophenotype, highlighting its heritability, state-independence, and familial association. Behavioral studies show that depressed individuals exhibit reduced affective responses to positive cues, impaired encoding and retrieval of positive information, and diminished ability to modulate behavior based on reinforcement. Neuroimaging studies reveal reduced activation in reward-related brain regions in depressed individuals. The role of dopamine in depression is explored through studies on DA metabolites, DA depletion, and molecular imaging, suggesting reduced DA transmission. The paper also reviews the role of stress in the development and exacerbation of depression, noting that chronic and uncontrollable stressors are particularly depressogenic. Finally, the effects of stress on dopaminergic pathways are discussed, with acute stressors activating mesocorticolimbic DA neurons and chronic stressors blunting DA release in these pathways.