Hypoactive sexual desire (HSD) is defined as persistently or recurrently deficient (or absent) sexual fantasy and desire for sexual activity, leading to marked distress or interpersonal difficulty (DSM IV). This psychiatric definition excludes HSD when is secondary to other medical disorders. However, HSD is often found in patients affected with other conditions, as erectile dysfunction (ED), thus determining a complex sexual disorder which is very challenging to the physician. As a matter of fact, prevalence rates of HSD are similar to what reported for ED, ranging from 5 to 15% in population based studies and the fact that many more patients worldwide are currently treated for ED than for HSD raises more than a question. HSD, rather than being accountable only to psychiatric disorders in otherwise “organically” healty individuals, in a vast majority of cases is associated to medical condition where the biologic component of sexual desire is disregulated. Testosterone deficiency is currently the most carefully investigated medical syndrome to which both HSD and ED are associated. However, other hormonal (like hyperprolactinemia, hyper- and hypothyroidism) and non-hormonal abnormalities are involved in a significant percentage of patients. Diagnosis of biologic component of HSD is sometimes difficult because of the lack of a precise threshold for the hormonal serum level associated to clinical evidence of diminished sexual desire. Currently used cut-offs should be re-discussed at the light of recent evidences from literature.