This chapter examines the current and new methods available to diagnose and select the best sperm to fertilize the egg. Preparation of sperm with media containing antioxidants has shown improvement in the overall functional parameters of the spermatozoa and reduction in the ROS level. This may improve the quality of gametes used for protecting the spermatozoa from high oxidative stress. A novel and promising technique of annexin V-conjugated microbeads (ANMB), magnetic-activated cell sorting (MACS) has been shown to remove spermatozoa with phosphatidylserine externalization (marker of apoptosis) and produce a higher-quality non-apoptotic sperm fraction. Furthermore, these negative-apoptotic marker cells display higher fertilization rates when used for animal model in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI). A number of studies have now indicated that hyaluronic acid (HA)-bound sperm used in the ICSI procedure may lead to increased implantation rates.