Polyploidy appears to have played a limited role in citrus germplasm evolution. However, today, ploidy manipulation is an important component of citrus breeding strategies. For varieties, the main objective is to develop triploid seedless cultivars. For rootstock, the aim is to cumulate interesting traits in tetraploid hybrids and to improve adaptation to biotic and abiotic stresses. This chapter starts with a review of the recent knowledge acquired on the natural mechanisms of citrus polyploidization and tetraploid meiosis. Chromosome doubling of nucellar cells is frequent in apomictic citrus and results in tetraploid seedling production. Unreduced gametes are also frequently produced, mainly by second division restitution for ovules. First division restitution was described for pollen as well as alternative mechanisms for both ovules and pollen. Tetraploid plants display tetrasomic to disomic segregations in relation to their genome structure (autotetraploid versus allotetraploid) and the divergence of the parental species. The implications of the origin of diploid gametes, on the genetic diversity of polyploid progenies, are discussed. The biotechnological tools (haplomethods, chromosome doubling by chemical treatments, somatic hybridization, and cytogenetic/molecular tools for polyploid genome studies) used to optimize ploidy manipulation are presented. The interest of haploid and polyploid genotypes for basic genetic and genomic studies is discussed. The research areas reviewed are as follows: haploids and doubled haploids for genome sequencing and haplotyping, centromere mapping from unreduced gametes, marker–trait association study in polyploids, and phenome and gene expression in polyploids with a special focus on polyploidy and adaptation. Finally, we give an overview of the recent advances of concrete polyploid citrus breeding programs in China, Florida, and the Mediterranean Basin.