In the era of orally active agents the clinical context of the diagnosis and treatment of erectile dysfunction (ED) has radically changed. There is a general trend oriented towards choosing invasive diagnostic testing and surgical treatment solutions. Along this view, penile pharmacotesting (PPT) may represent an inexpensive and easy diagnostic procedure to be performed in the office setting. However, this procedure provides no direct vascular imaging, has a high percentage of false diagnoses and its accuracy for subsequent treatment decisions remains quite limited. Hence, home testing with orally active agents may provide better information for the patient's goals. In the diagnostic work-up of ED, the combination of PPT plus colour-duplex Doppler ultrasonography (CDDU) has gained more credit because of a higher diagnostic accuracy than PPT alone, so that it should be always performed when possible. It represents an accurate mean to predict cavernous artery inflow and venous leakage when compared to more invasive diagnostic techniques; in fact it allows the measurement of the resistive index when maximal response to vasodilator challenge has occurred. In conclusion, we recommend CDDU to all ED patients with a significant risk of cardiovascular disease, as well as in the presence of penile plaques whereas a frequent involvement of neuro-anatomical structures occurs. Other vascular testing--i.e. natural penile tumescence, cavernosometry/graphy, angiography are reserved to selected patients in whom CDDU alone has provided inconsistent information.