Increase in life expectancy worldwide is associated with a higher prevalence of stress-linked neuropsychiatric illnesses such as depression. Age-related alterations in neuroendocrine axes could contribute to the appearance of affective disorders and changes in response to conventional antidepressants. This review analyzes, in aged male rats, the role of testosterone in stress vulnerability, response to citalopram, and modulation of the expression of its pharmacologic target: brain serotonin transporter. In comparison with younger males, older hypogonadal males are more vulnerable to the chronic mild stress paradigm because they express higher rates of anhedonia, an effect that is prevented by restitution with testosterone. Resilience to chronic mild stress induced by testosterone seems to be associated with its inhibitory actions on hypothalamus-pituitary-adrenal axis function. In contrast with young males, aged males have reduced levels of serotonin transporter and exhibit slower antidepressant response to citalopram in chronic mild stress. Interestingly, testosterone restitution in older rats increases serotonin transporter expression in dorsal raphe nucleus, suggesting that this androgen plays a regulatory role in the actions of serotonergic antidepressants. Experimental studies lead to regard hypogonadism as a factor in the etiology of affective disorders and suggest that testosterone restitution should improve antidepressant response in later-life depression.