Hypertrophic cardiomyopathy (HCM) is a global and relatively common cause of patient morbidity and mortality and is among the first reported monogenic cardiac diseases. For 30 years, the basic etiology of HCM has been attributed largely to variants in individual genes encoding cardiac sarcomere proteins, with the implication that HCM is fundamentally a genetic disease. However, data from clinical and network medicine analyses, as well as contemporary genetic studies show that single gene variants do not fully explain the broad and diverse HCM clinical spectrum. These transformative advances place a new focus on possible novel interactions between acquired disease determinants and genetic context to produce complex HCM phenotypes, also offering a measure of caution against overemphasizing monogenics as the principal cause of this disease. These new perspectives in which HCM is not a uniformly genetic disease but likely explained by multifactorial etiology will also unavoidably impact how HCM is viewed by patients and families in the clinical practicing community going forward, including relevance to genetic counseling and access to healthcare insurance and psychosocial wellness.