Successful salmonid restoration efforts depend upon an understanding of the evolutionary processes that historically shaped population diversity, as well as the realities of currently available, altered river systems. Habitat alterations over the past century have dramatically changed the ecological forces that shaped salmonid speciation and evolution, bringing formerly separate and distinct populations into contact and in some cases leading to hybridization. Hybridization can threaten the genetic diversity within salmonid species and may affect the outcomes of restoration efforts. Here we use the San Joaquin River Restoration as a case study to discuss some of the genetic challenges of Chinook salmon restoration in a newly reopened habitat. We discuss a range of genetic management strategies—from passive reintroduction to tightly managed, active reintroduction—and the strengths and weaknesses of each approach.