Comparative genetics provides veterinary researchers and clinicians with invaluable information for the understanding the possible genetic aetiologies and the disease process in congenital heart defects (CHDs) of dogs and cats. Although, the demand on this type of research has increased in the veterinary field, to date no fundamental genetic studies have been reported in the veterinary literature. In this second part of a two-part review, the general features and pathogenesis of major CHDs in humans and small animals are discussed. In addition, the known genetic aetiologies in human CHDs have been considered in parallel to CHDs in small animals.