Erectile dysfunction (ED), defined as the inability to achieve and/or maintain an erection sufficiently long for a satisfactory sexual performance or intercourse, is an important and common medical problem. ED is not a life-threatening disorder, but it influences the daily routine, social interactions, well-being and quality of life of the patient. Recent epidemiological data have shown a high prevalence and incidence of ED. The Massachusetts Male Aging Study found that 52% of men between the ages of 40 and 70 years reported ED with 9.6% having mild, 22.2% moderate and 17.2% complete or severe ED. In a large Italian cross-sectional study the overall prevalence of self-reported ED was 12.8% and the frequency of ED increases with age. ED may signal serious underlying and potentially life-threatening diseases, such as diabetes, hypertension, cardiovascular disease, peripheral vascular disease and other neurological and endocrine disorders. Also well documented is the role of some drug groups, certain types of surgery, injuries and the role of risk factors related to lifestyle such as smoking, alcohol consumption and inappropriate dietary habits accompanied by an abnormal serum level of cholesterol. The current availability of effective and safe oral drugs for ED in conjunction with the tremendous media interest in the condition, have resulted in an increasing number of men seeking help for ED. As a consequence, many physicians without background knowledge and clinical experience in the diagnosis of ED are involved in making decisions concerning the evaluation of such patients. The result of this is that some males with ED may undergo little or no evaluation before treatment is initiated and, in such circumstances, the disease causing the symptom (ED) may remain untreated. Baseline diagnostic evaluation for ED can identify the underlying pathological condition or the risk factors associated with ED in 80% of patients. This article reports a sequential approach for the diagnosis of ED that may diagnose reversible causes of ED and also unmask medical conditions that manifest with ED as the first symptom.