Depression and fibromyalgia syndrome are debilitating chronic conditions that impose a significant burden on individuals, families and society. Both depression and fibromyalgia have many overlapping symptoms, and antidepressants of several classes are among recommended treatment options for patients with fibromyalgia syndrome. Pirlindole is a selective and reversible inhibitor of monoamine oxidase (MAO) subtype A (MAO-A) that is approved in some European and non-European countries for the treatment of depression. The antidepressant efficacy and safety of pirlindole have been demonstrated in a number of placebo- and active comparator-controlled studies and are supported by many years of clinical experience in the treatment of depression. The drugs efficacy and safety have also been demonstrated, more recently, in the treatment of fibromyalgia syndrome. Pirlindole has a favourable tolerability profile, with no deleterious effect on cardiovascular dynamics. The effect of pirlindole on sensorimotor performance relevant to driving a motor vehicle is similar to that of placebo, as pirlindole appears to have an activating rather than a sedating antidepressant profile. Because of its specific and reversible inhibition of MAO-A and relatively short elimination half-life, no tyramine or 'cheese' effect is likely after short- or long-term administration. The available evidence supports pirlindole as a safe and effective treatment option for the management of depression and fibromyalgia syndrome.