Monoamine oxidase inhibitors (MAOIs) are a class of drug that inhibit the activity of one or both monoamine oxidase enzymes: monoamine oxidase A (MAO-A) and monoamine oxidase B (MAO-B). MAOIs are effective antidepressants due to their specialized function of the inhibition of the enzyme that is responsible for neurotransmitter degradation in the synaptic cleft. This is especially true for treatment-resistant depression, which is a type of depression that is resistant to common treatments of typical depression, such as selective-serotonin reuptake inhibitors (SSRIs) or serotonin-norepinephrine reuptake inhibitors (SNRIs).

MAOIs are also utilized to treat panic disorder, social anxiety disorder, Parkinson's disease, and several other disorders.

Reversible inhibitors of monoamine oxidase A (RIMAs) are a subclass of MAOIs that selectively and reversibly inhibit the MAO-A enzyme. RIMAs are used clinically in the treatment of depression and dysthymia. Due to their reversibility, they are safer in single-drug overdose than the older, irreversible MAOIs, and weaker in increasing the monoamines important in depressive disorder. RIMAs have not gained widespread market share in the United States.

MAOIs have been found to be effective in the treatment of panic disorder with agoraphobia, social phobia, atypical depression or mixed anxiety disorder and depression, bulimia, and post-traumatic stress disorder, as well as borderline personality disorder, and obsessive–compulsive disorder (OCD). MAOIs appear to be particularly effective in the management of bipolar depression according to a retrospective-analysis from 2009. There are reports of MAOI efficacy in OCD, trichotillomania, body dysmorphic disorder, and avoidant personality disorder, but these reports are from uncontrolled case reports.

MAOIs can also be used in the treatment of Parkinson's disease by targeting MAO-B in particular (therefore affecting dopaminergic neurons), as well as providing an alternative for migraine prophylaxis. Inhibition of both MAO-A and MAO-B is used in the treatment of clinical depression and anxiety.

MAOIs appear to be particularly indicated for outpatients with dysthymia complicated by panic disorder or hysteroid dysphoria.

Newer MAOIs such as selegiline (typically used in the treatment of Parkinson's disease) and the reversible MAOI moclobemide provide a safer alternative and are now sometimes used as first-line therapy.

Pargyline is a non-selective MAOI that was previously used as an antihypertensive agent to treat hypertension (high blood pressure).