Central serotonergic (5-HT) and noradrenergic (NA) neurons, which innervate the same regions of the brain, are known to play a crucial role in emotion and mood. These monoamine neurons have a great capacity to alter axonal morphology in response to repeated stress. The morphological responses of 5-HT and NA axons to repeated stress are different, and they sometimes even demonstrate opposite responses (namely, either sprouting or degeneration). Moreover, a morphological interaction also occurs between 5-HT and NA axons during axonal regeneration. This review describes the differential features of axonal plasticity of 5-HT and NA neurons in relation to stress, and discusses the possible roles that the morphological plasticity of 5-HT and NA axons may play in the pathophysiology of depression.