<p>The diagnosis of infertility requires a multidisciplinary approach that involves both partners, in order to identify the causes and provide the most appropriate therapeutic options, limiting when possible the use of unnecessary invasive and expensive procedures. In particular, a complete diagnostic workup for male factor infertility (MFI) allows for classification of patients into one or more of the following diagnostic classes: infection and inflammation of the accessory sexual glands; ductal obstruction/agenesis/retrograde ejaculation; primary testicular damage; secondary testicular dysfunction; varicocele; idiopathic alterations of the seminal parameters; unexplained infertility. In relation to the underlying picture, therefore, aetiological or empirical treatments can be carried out, which are the subject of the following article. Antibiotics are the main treatment for bacterial infections. Therapy should be based on the identification of the pathogen and determination of antibiotic sensitivity by antibiogram. In case of leukocytospermia or in the presence of other inflammatory signs at the seminal level or signs at the ultrasound level, without isolation of pathogens, empirical therapy can be adopted with nonsteroidal anti-inflammatory drugs or corticosteroids, administered orally or transrectally. Gonadotropin therapy represents the therapy with the highest level of evidence of efficacy in the field of MFI. Classically, gonadotropin therapy is used in hypogonadotropic hypogonadism, with excellent response both in terms of improvement of seminal parameters and in terms of spontaneous pregnancy. On the basis of these assumptions, FSH therapy is proposed from many years in infertile male patients, with seminal picture of oligozoospermia and/or asthenozoospermia, in the presence of FSH levels lower than 8 IU/L and in the absence of obstructive picture at the seminal duct level. In this situation, the therapy induces a significant improvement in the number and motility of spermatozoa and an improvement in the rate of spontaneous and post-assisted reproduction technique pregnancies. Selective oestrogen receptor modulators (SERMs) and aromatase inhibitors (IAs) represent possible off-label therapies, although their use is not supported by strong evidence and their use is not recommended by the most recent guidelines. Moreover, all studies agree in highlighting how the possible efficacy of the therapy is associated with a further increase in FSH levels, thus suggesting that a hyperstimulatory strategy with FSH could be associated with further improvement in seminal parameters even in patients with FSH higher than 8 IU/L. Although varicocele is very frequent in the general population and in infertile subjects, its clinical value in the management of infertility is limited. The diagnosis of varicocele as a real cause of infertility therefore represents a diagnosis of exclusion, to be considered especially in the presence of varicocele with numerous and/or large venous ectasias and significantly increased reflux, without other known causes of infertility. The use of supplements and nutraceuticals to improve male fertility is still a highly debated topic. Current guidelines reiterate that prescription is not indicated before the implementation of a diagnostic pathway. At the same time, the challenge in this area remains customisation, for a possible evidence-based use of nutraceuticals in patients with infertility and conditions associated with oxidative stress.</p>