Introduction. Acute myocarditis is defined by the presence of inflammation of the myocardium, triggered mainly by viral factors. International statistical reports determined a global annual incidence of about 1.5 million cases for all age groups. Clinically, it is a polymorphic disease, both in presentation and clinical evolution. Recent publications suggest that the particular genetic background, interacting with epigenetic factors, could be determinants in the initial clinical scenario and evolution towards dilated cardiomyopathy (CMD). The objective of this review is to present the current scientific evidence in elucidating the role of the genetic substrate in the initiation and natural history of acute myocarditis. Material and methods. We used the PubMed and ScienceDirect databases, with a selection of articles, consensus documents and international guidelines published during the last 10 years. Results. Recent studies have hypothesized that genetic defects responsible for the protein structure of the cardiomyocyte could result in a vulnerable myocardium, prone to myocardial inflammation and subsequently to CMD or arrhythmogenic cardiomyopathy. The available evidence regarding immune reactions and genetically determined host factors is conflicting. A recent study by Belkaya et al. was able to demonstrate the interrelationship between mutations in the TLR3 and STAT1 genes and increased susceptibility to the onset of viral myocarditis. Several researchers have reported the results of clinical trials, where multiple pathogenic/ probably pathogenic genetic variants were confirmed in 30% of patients, among which titin, dystrophin and desmoplakin protein mutations were found to be predominant. Other authors believe that the viral-immune complex process could be like a trigger in the development of cardiomyopathies in other genetic conditions. Supplementing the evidence in favor of the concept of a complex interaction between pathogenic genetic variants, viral causative factors and epigenetic factors could change the approach to patients with acute myocarditis. Conclusions. There is currently increasing evidence regarding the role of genetics in both the susceptibility and the development of myocarditis. This evidence explains the clinical evolution variability of myocarditis and would allow personalized cardiovascular risk stratification of patients.