The morphological and biochemical characteristics of the acrosome depart well from any other vesicles in somatic cells, making it one of a kind amongst secretory vesicles. The components of the acrosome include a mixture of unique enzymes like acrosin and other enzymes that when present in somatic cells are commonly found in lysosomes, peroxisomes, and even in the cytoplasm. Several observations have pointed out that acrosomal biogenesis has unique features not previously described in secretory vesicle biogenesis of somatic cells. In this review we discuss the evidence supporting a molecular link between the machinery involved in lysosome and acrosome biogenesis, link which may help account for the acrosome unique composition.