Mirtazapine belongs to the category of antidepressants clinically used mainly in major depressive disorder but also used in obsessive-compulsive disorders, generalized anxiety, and sleep disturbances. This drug acts mainly by antagonizing the adrenergic α2, and the serotonergic 5-HT2 and 5-HT3 receptors. Neuropsychiatric symptoms, such as depression and agitation, are strongly associated with Alzheimer's disease, reducing the life quality of these patients. Thus, it is crucial to control depression in Alzheimer's patients. For this purpose, drugs such as mirtazapine are important in the control of anxiety, agitation, and other depressive symptoms in these patients. Indeed, despite some contradictory studies, evidence supports the role of mirtazapine in this regard. In this review, we will focus on depression in Alzheimer's disease, highlighting the role of mirtazapine in this context.