Infertility is a condition that widely affects couples all over the world. In this regard, sperm DNA fragmentation can lead to harmful reproductive consequences, including male infertility and poor outcomes after assisted reproductive techniques. The investigation of sperm DNA fragmentation in male infertility diagnostics has constantly increased over time, becoming more common in clinical practice with the recent publication of several guidelines regarding its testing. This narrative review aims to provide a comprehensive overview of the pathogenesis and causes of sperm DNA fragmentation, as well as the assays which are commonly performed for testing. Moreover, we discuss the most recently published evidence regarding the use of sperm DNA fragmentation testing in clinical practice, highlighting the implications of high sperm DNA fragmentation rate on human reproduction, and the therapeutic approaches for the clinical management of infertile patients. Our review confirms a significant harmful impact of sperm DNA fragmentation on reproduction and points out several interventions which can be applied in clinics to reduce sperm DNA fragmentation and improve reproductive outcomes. Sperm DNA fragmentation has been shown to adversely impact male fertility potential. As high sperm DNA fragmentation levels have been associated with poor reproductive outcomes, its testing may significantly help clinicians in defining the best therapeutic strategy for infertile patients.