Restoration of shellfish populations is becoming an increasingly common practice worldwide, as natural fisheries succumb to pressures of overharvesting, habitat loss or degradation, and challenges from invasive competitors and pathogens. Primary genetic concerns relevant to shellfish restoration projects are reviewed, using the cupped oysters Crassostrea gigas and Crassostrea virginica as case studies. Molecular genetic tools can be used to delineate the geographic distribution of germ plasm diversity at the species and intraspecific levels, enabling more informed selection of genetic material for hatchery breeding and production. Maintenance of genetic variability and prevention of excessive inbreeding in hatchery stocks may be facilitated by the use of genetic markers for regular pedigree monitoring. The effect of hatchery supplementation on the effective population size of a recipient wild population (Ryman-Laikre effect) is reviewed in light of the population biology of bivalve molluscs, and appears to be minimal. Deployment of selected enhancement stocks may be a valuable tool for improvement of degraded wild populations, reversing the negative effects of generations of selective harvesting. Molecular genetic tools can be used effectively to monitor restoration programs, when the discriminatory power of the marker(s) is high and high-throughput scoring methods currently available are used.