The global burden of erectile dysfunction (ED) is increasing. It is estimated that 8–19% of men in Europe have ED and that by 2025 the prevalence of ED worldwide will reach 322 million. The gold standard therapy for ED is an oral phosphodiesterase type 5 (PDE5) inhibitor, but they are not suitable for everyone; approximately 25% of patients do not respond to this therapy and it is contraindicated in others, e.g. those with vascular disease. When PDE5 inhibitors are not suitable, available options include intraurethral and intracavernosal alprostadil – a synthetic vasodilator chemically identical to the naturally occurring prostaglandin E1 indicated for the treatment of ED. Intraurethral alprostadil is delivered by the Medicated System for Erection (MUSE).– a single-use pellet containing alprostadil suspended in polyethylene glycol administered using an applicator. It is recommended that intraurethral alprostadil be initiated at a dose of 500 μg, as it has a higher efficacy than the 250 μg dose, with minimal differences with regard to adverse events. Data from key clinical studies of intraurethral alprostadil show that it has a fast onset of effect and a good safety profile, with no occurrences of priapism, fibrosis (as seen with intracavernosal injection) or the typical systemic effects observed with oral ED pharmacological treatments. Intraurethral alprostadil has been associated with high patient preference, acceptance rates and quality of life versus intracavernosal injection due to its ease of administration. Evidence has shown that combination treatment with sildenafil may be a possible efficient alternative when single oral or local treatment has failed. Intraurethral alprostadil can be administered in all patients irrespective of ED origin and should be the first option in patients with ED for whom therapy with PDE5 inhibitors has failed or is contraindicated.