The following chapter is an attempt to understand the diagnosis of unexplained infertility (UI) in current practice and the management thereof. Unexplained infertility continues to confound and challenge fertility specialists world over. Clinical experience and research has over the years implicated many a factors as the possible cause of subfertility in these cases, however, most have not shown any direct correlation with fecundity. Conception is by far one of the most elaborate and magnificent choreographies of nature with each component working in complete harmony and synchrony with the other. This chapter covers the unexplained male infertility, female infertility, and management. Male partners who have a normal medical history, normal physical examination, a semen analysis reported as normal and in whose partner no female factors have been identified are classified as having unexplained male infertility (UMI). Possible factors leading to UMI may be the presence of antisperm antibodies (ASAs), sperm DNA damage, elevated levels of reactive oxygen species (ROS), genetic defects, and sperm dysfunction.