The spermatozoa of vertebrate species that practice internal fertilization have to transit along the epididymis after leaving the testis. This epididymis is a single, long convoluted tubule that links the testis to the vas deferens (1). During this transit, the male gametes acquire their fertilizing ability and their forward motility properties. Collectively, these modifications known as sperm maturation depend on a series of well-orchestrated biochemical modifications imposed upon the transiting male gamete (2). These modifications are in part regulated by extracellular microvesicles called epididymosomes that are found in the intraluminal epididymal compartment (3, 4). In this review, the biochemical composition of epididymosomes, their mode of secretion, the mechanisms underlying their interactions with the male gamete, and how they are involved in sperm maturation will be described.