Midodrine is a prodrug which undergoes enzymatic hydrolysis to the selective alpha 1-adrenoceptor agonist desglymidodrine after oral administration. Oral midodrine significantly increases 1-minute standing systolic blood pressure compared with placebo. The drug also improves standing time and energy level and clinical symptoms of orthostatic hypotension including dizziness, light-headedness and syncope. Comparative studies have shown midodrine to have similar efficacy to dihydroergotamine mesylate, norfenefrine, fludrocortisone and etilefrine, and to be more effective than dimetofrine and ephedrine in patients with orthostatic hypotension. Midodrine is well tolerated, with the most commonly reported adverse events being piloerection, pruritus, paraesthesias, urinary retention and chills. The risk of supine hypertension, which is associated with midodrine therapy in up to 25% of patients, can be reduced by taking the final daily dose at least 4 hours before bedtime. Thus, oral midodrine is an effective therapeutic option for the management of various forms of orthostatic hypotension. This well-tolerated agent is likely to be useful in conjunction with standard nonpharmacological care.