Human sperm has functional domains on the head and tail (flagellum). Since functional molecules are organized into the substructures of these domains, sperm with good appearance are expected to be fertile. Thus, it is of interest to see how sperm fine morphologies relate to fertility. The sperm head is divided into the acrosome and postacrosome regions. The acrosome region is further divided into the anterior acrosome for the acrosome reaction and posterior acrosome (equatorial segment) for gamete membrane fusion. The postacrosome region is involved in egg activation. In addition, the human sperm head has varieties of nuclear vacuoles. High-resolution light microscopy, which has recently been used in IMSI (intracytoplasmic morphologically selected sperm injection), is helpful in identifying vacuoles. However, IMSI is still insufficient for analysis of the contents of vacuoles; electron microscopy and evaluation tests for sperm DNA damage are more helpful for profound analysis of the nature of nuclear vacuoles and DNA status, respectively. The neck region carries the paternal centrosome to the oocyte to evoke sperm aster, from which microtubules emanate. Organization failure of the midpiece and principal piece strongly affects motility. This paper discusses the relationship beween the normality/abnormality of sperm substructures and fertility and shows typical phenotypes found in gene knockout animal models.