Clinical and molecular genetics are inextricably linked. In the last two decades genetic studies have revealed the causes of several forms of structural heart disease. Recent work is extending the insights from inherited arrhythmias and cardiomyopathies to other forms of heart disease. In this review we outline the current state of the art for the genetics of adult structural heart disease, in particular the cardiomyopathies, valvular heart disease and aortic disease. The general approaches are described with a focus on clinical relevance, while potential areas for imminent innovation in diagnosis and therapeutics are highlighted.