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The diagnosis of unexplained infertility can be made only after excluding common causes of infertility using standard fertility investigations, which include semen analysis, assessment of ovulation, and tubal patency test. These tests have been selected as they have definitive correlation with pregnancy. It is estimated that a standard fertility evaluation will fail to identify an abnormality in approximately 15% to 30% of infertile couples. The reported incidence of such unexplained infertility varies according to the age and selection criteria in the study population. We conducted a review of the literature via MEDLINE. Articles were limited to English-language, human studies published between 1950 and 2013. Since first coined more than 50 years ago, the term unexplained infertility has been a subject of debate. Although additional investigations are reported to explain or define other causes of infertility, these have high false-positive results and therefore cannot be recommended for routine clinical practice. Couples with unexplained infertility might be reassured that even after 12 months of unsuccessful attempts, 50% will conceive in the following 12 months and another 12% in the year after.Obstetricians and gynecologists, family PhysiciansAfter completing this CME activity, physicians should be better able to identify the epidemiology of unexplained infertility and standard investigations for infertile couples and to consider other possible causes of infertility before making a diagnosis of unexplained infertility.