Despite significant advances in the field of genetic cardiomyopathies, the treatment of inherited cardiac disease has long focused on symptom management and therapies geared towards the consequences of heart failure. More recently, small molecule therapy has emerged as a targeted approach that seeks to alter the progression of genetic cardiac disease at the molecular level. To provide a summary of the novel therapeutics in primary genetic cardiomyopathies. Small molecule myosin inhibitors have been developed to decrease the hypercontractility observed in conditions like hypertrophic cardiomyopathy and myosin activators seek to reverse the reduced left ventricular function seen in dilated cardiomyopathy. Further targeting specific genetic etiologies of cardiomyopathy, P38α MAP kinase inhibition is a therapy developed to counter abnormally upregulated pathways in lamin A/C cardiomyopathy. While trials are still ongoing, these small molecule therapies could alter the treatment landscape of genetic cardiomyopathies for years to come •Small molecule therapy has emerged as a targeted approach to alter the progression of genetic cardiac disease at the molecular level.•Myosin activation seeks to reverse the reduced left ventricular function seen in heart failure with reduced ejection fraction.•Myosin inhibition aims to decrease the hypercontractility observed in conditions like hypertrophic cardiomyopathy.•Small molecule therapies could alter the treatment landscape of genetic cardiomyopathies for years to come.