A substantial body of research shows that elevated sperm DNA fragmentation (SDF) tends to be related to both natural conception likelihood and outcomes in assisted-reproduction settings, although conflicting results are frequently reported. High SDF has been linked in several works to reduced pregnancy and delivery rates after intrauterine insemination (IUI) and to lower fertilization, implantation, pregnancy, embryo-quality, and live-birth rates in conventional in vitro fertilization (IVF) under the conventional way of measuring ART success. Nevertheless, effect’s size is enormously variable, and the real impact is yet uncertain. While high SDF does not appear to diminish fertilization or overall pregnancy rates per embryo transfer after intracytoplasmic sperm injection (ICSI) or cumulatively, it is associated with poorer embryo quality and a higher risk of miscarriage. To counteract these effects, several sperm-selection strategies, based on different sperm characteristics associated with higher DNA fragmentation, such as magnetic-activated cell sorting (MACS) for apoptotic sperm, intracytoplasmic morphologically selected sperm injection (IMSI) for sperm with subtle morphological abnormalities, physiologic ICSI (P-ICSI) for immature sperm, and microfluidic sperm sorting among other few, have been developed to enrich for spermatozoa with less affected DNA before its use in assisted reproductive techniques (ART). This chapter examines, based on the most recent evidence, on how high SDF in infertile men influences IVF/ICSI outcomes and summarizes the principles, benefits, and limitations of current methods for selecting sperm with optimal DNA integrity to be utilized in ART.