Recent studies of centrosome biogenesis, microtubule dynamics, and their management point to their role in mediating conditions such as aging and cancer. Centrosome dysfunction is also a hallmark of pathological polyspermy. Polyspermy occurs when the oocyte is penetrated by more than one sperm and can be pathological because an excess of centrosomes compromises development. However, in some taxa, multiple sperm enter the egg with no apparent adverse effect on zygote viability. Thus, some taxa can manage excess centrosomes and represent cases of non-pathological polyspermy. While these two forms of polyspermy have long been known, we argue that there is limited understanding of the proximate and ultimate processes that underlie this taxonomic variation in the outcome of polyspermy and that studying this variation could help uncover the control and role(s) of centrosomes during fertilization in particular, but also mitosis in general. To encourage such studies we: 1) describe taxonomic differences in the outcome of polyspermy, 2) discuss mechanistic aspects of reproductive biology that may contribute to the different consequences of polyspermy, and 3) outline the potential selective events that could lead to the evolution of variation in polyspermy outcomes. We suggest that novel insights into centrosome biology may occur by cooperative studies between reproductive and evolutionary biologists focusing on the mechanisms generating variation in the fitness consequences of polyspermy, and in the taxonomic distribution of all these events. The consequent discoveries of these studies may lead to informative insights into cancer and aging along with other centrosome-related diseases and syndromes.