In this review, the structural and functional characteristics of the human epididymis, including vas efferents and ductus deferens, are revisited under the morphological and ultrastructural point of view. New surface sperm antigens, enabling the fertilizing power during the epididymal transit, various epididymal microenvironments and their activities on the spermatozoa are reported. This revision is important because the recent procedures of assisted reproduction, aimed at overcoming the cases of obstructive azoospermia, use the spermatozoa aspirated from the proximal segments of the epididymis and suggest a flexibility of the epididymal function with regard to the fertilizing sperm capacity. In my opinion these procedures must be based on an accurate investigation on the function of the different epididymal districts. Moreover, in patients affected by congenital absence of the vas deferens (CAV), the ultrastructural examination of the spermatozoa aspirated from the proximal segments of the epididymis revealed that most of them are defective: in fact the absence of the vas deferens seems to affect the development and the functional properties of the epididymal spermatozoa.