The treatment for depression in primary care begins with detecting patients with depression among patients who complain physical symptoms. It is recommended to use screening tests in high-risk groups in order to increase efficiency. Measurement-based care is useful because it systematically uses verified assessment tools to assess severity and monitor treatment progress. Selective serotonine reuptake inhibitors (SSRIs), serotoninenorepinephrine reuptake inhibitors (SNRIs), mirtazapine, and vortioxetine are recommended as first-line drugs for treating major depressive disorder. Drug treatment consists of antidepressant monotherapy or combination therapy. The goal of acute phase pharmacotherapy is symptomatic remission in 6–12 weeks. The continuation phase corresponds to 4–9 months after acute phase, and the goal is to maintain the state of remission and prevent relapse. If symptoms do not improve within 2–4 weeks after starting antidepressants, the dose is optimized or increased. If there is no response after 4 weeks at the appropriate dose or tolerance is an issue, a different antidepressant should be prescribed. If antidepressant monotherapy is ineffective or anxiety, insomnia, pain, etc. are present, benzodiazepines, buspirone, nonsteroidal anti-inflammatory drugs (NSAIDs), estrogen, testosterone, etc. are added as augmentation, or a different class of antidepressants are combined. When remission continues for more than 6 months after antidepressant treatment and drug treatment is to be discontinued, antidepressants with a short half-life should not be discontinued abruptly.