Sperm membranes have an unusual lipidic composition which is distinct from those of mammalian somatic cells. They have high levels of plasmalogens, a kind of ether-linked lipids, and a high content of polyunsaturated fatty acyl groups. Plasmalogens may form non-diffusible membrane regions or domains, whereas polyunsaturated ethanolamine plasmalogens are known to destabilize the lipidic bilayer. During transit of sperm through the female reproductive tract, sperm-coating proteins bind to heparin-like glycosaminoglycans. An essential feature of capacitation is the removal of cholesterol from the acrosomal membrane of sperm. Albumin and high-density lipoproteins present in the uterine and follicular fluid act as cholesterol acceptors. Plasma membrane of sperm organize in large non-diffusible lipid domains. This regionalization affects the distribution of both lipids and proteins. A barrier to lateral diffusion of lipids and proteins in the equatorial segment has been reported and contributes to the formation of macrodomains. Lateral separation into cholesterol-rich and cholesterol-depleted microdomains could also be created. Cone-shaped phospholipids induce the formation of non-bilayer phases and might facilitate membrane fusion. This review will discuss the removal of coating proteins, cholesterol efflux, domain organization, relocalization of lipids and proteins and the role of fusogenic lipids during capacitation.