Three principal types of chromosomal sex determination are found in nature: male heterogamety (XY systems, as in mammals), female heterogamety (ZW systems, as in birds), and haploid phase determination (UV systems, as in some algae and bryophytes). Although these systems share many common features, there are important biological differences between them that have broad evolutionary and genomic implications. Here we combine theoretical predictions with empirical observations to discuss how differences in selection, genetic properties and transmission uniquely shape each system. We elucidate how the differences among these systems can be exploited to gain insights about general evolutionary processes, genome structure, and gene expression. We suggest directions for research that will greatly increase our general understanding of the forces driving sex-chromosome evolution in diverse organisms.