Significant, yet highly individual, thrombotic and inflammatory responses to surgery provide an excellent opportunity for insight into the genomic impact upon a patient's postoperative course. Cardiac surgery elicits the most profound perioperative disturbance and is associated with the highest incidence of adverse outcomes of any elective surgical procedure. Thus, cardiac surgical patients are an ideal population in which to evaluate the influence of complex traits on perioperative morbidity and mortality. This review describes the application of fundamental genetics upon the occurrence of adverse outcomes after cardiac surgery and cardiac transplantation. Specific emphases include a brief primer of the principles of genetics concentrating on the effects of variation within the human genome upon clinical outcomes and the differences between so-called Mendelian traits and complex traits. Four important clinical diseases dealt with in this review as examples of the impact of genetic factors on clinical outcomes are the genetics of heparin-induced thrombocytopenia, heart transplantation rejection and vasculopathy, atrial fibrillation, and infection.