Late-onset hypogonadism (LOH) is a clinical and biochemical syndrome associated with advancing age and characterised by typical symptoms together with a deficiency in serum testosterone levels. Identification of LOH-related symptoms and signs is, therefore, essential for suspecting this condition. We investigated a specific association between indicative signs and symptoms of androgen deficiency and its biochemical correlates (total T below 12 and/or 8 nmol/l) in a large series (2817) of patients consulting our Sexual Dysfunction Unit. In addition, a systematic review of the literature using Medline (1969 to March 2009) was also performed. We found that although structured interviews, such as ANDROTEST or other self-reported questionnaires, might help physicians to familiarise themselves with hypogonadal symptoms and suspect LOH, LOH-related symptoms and signs are rather non-specific, as they are also characteristic of the ageing process per se. We confirmed that an accurate focused clinical history (inquiring about cryptorchidism, pituitary diseases and delayed puberty) can be very informative about the presence of LOH. In addition, sex life-related performances (libido, erection and ejaculation) and attitudes (masturbation and extra-marital affairs) might also provide insights. Clinical signs, such as testis volume, penile blood flow and the presence of the metabolic syndrome, can also raise the suspicion of LOH: an increased waist circumference increases the risk of having LOH by a factor of 3. Although a clinical evaluation is mandatory in suspecting LOH, it is our opinion that the determination of total testosterone is essential in confirming the diagnosis and/or in starting any substitutive therapy.