Publisher Summary This chapter discusses the several recent reviews that cover various aspects of depression and antidepressant research. The research on selective inhibitors of serotonin (5HT) uptake relative to their effects on the uptake of dopamine (DA) or norepinephrine (NE) has led to the successful development of selective serotonin reuptake inhibitors (SRIs) as antidepressants. The results with fluoxetine seem to characterize the SRIs as a whole, efficacy equivalent to tricyclic antidepressants (TCAs), but often with better toleration because of a different spectrum of side effects. The advantage offered by fluoxetine, therefore, relates to a more benign side effect profile that makes it a more useful agent for some depressed patients. Semaline has proven to be a well tolerated and efficacious antidepressant in a number of trials and its preclinical biology has been reviewed. Paroxetine, one of the more potent 5HT uptake inhibitors in vitro , has shown antidepressant activity in a controlled clinical trial. It is also observed that SRIs produce positive results in treating obsessive compulsive disorder. Although one of the oldest classes of antidepressants, irreversible monoamine oxidase inhibitors (MAO), such as phenelzine and tranylcypromine, have had limited use because of a severe hypertensive crisis. However, recent reviews have appeared that cover the current biological understanding of MAO and the role of MAO inhibition in the treatment of depression. Current research now suggests that reversible and selective inhibition of MAO-A will afford antidepressant activity without hypertensive side effects. Buspirone, gepirone, SM-3997, and ipsapirone represent a new class of non-benzodiazepine anxiolytics that have also demonstrated promise as antidepressants. Further reports on rolipram, the prototype of this new class of antidepressants, have been encouraging. The potential for new therapies of depression and affective disorders has emerged from research around lithium, corticotropin-releasing factor (CRF), and S-adenosyl methionine.