Populus breeding is distinguished by a long history in forest tree improvement and its frequent dual reliance on inter-specific hybridization and varietal selection as the prominent domestication strategy. This chapter presents a review of the genecology and the principal long-term improvement approaches considered in the manipulation of the genus’ key taxa, the pertinent experimental design features of worldwide varietal evaluation programs, and the current understanding of the morphological, physiological, and pathology components of yield and the physical and chemical components of wood quality. The chapter concludes with an assessment of the molecular tools being developed for an integrated translational genomics program to improve upon present breeding and selection methodologies.