Major Depressive Disorder is a common psychiatric condition, and a leading cause of disability worldwide, affecting millions of individuals across diverse age groups and socioeconomic backgrounds. Fortunately, depression is highly treatable. Pharmacotherapy, certain forms of psychotherapy, and electroconvulsive therapy (ECT) all show antidepressant efficacy, leading to significantly improving patients' quality of life. However, despite the clear benefits of these treatments, many challenges and unanswered questions remain. A significant number of patients do not fully respond to available treatments. Even with aggressive treatment, up to 20% may show little or no improvement. Research into the neurobiological basis of mood disorders has made significant strides in recent decades, offering new insights into the neurochemical, neuroanatomical, and genetic factors underlying depression. This progress has opened promising new avenues for the development of more effective antidepressant treatments.