Performing regular resistance exercise training has been found to improve an individual’s health, including improved metabolism and ability to perform maximal contractile force in skeletal muscle. Certain epigenetic changes are believed to provide a positive impact on individuals and resistance exercise is also known to cause epigenetic changes to occur, including DNA methylation, changes in mRNA expression, differential microRNA expression, and histone modifications. There is debate as to whether these changes are beneficial but with chronic exercise, these changes do appear to provide a benefit to the individual. All these changes play a role in gene expression and the changes that occur with resistance exercise can possibly cause an advantage to an individual, such as increased insulin sensitivity and muscle hypertrophy. Possible mechanisms causing these changes in skeletal muscle include changes in calcium influx, ATP depletion, alterations in metabolic cycle intermediates, and oxidative stress. Understanding the mechanisms by which these changes occur in skeletal muscle due to resistance exercise can have implications in human medicine, such as interventions to treat metabolic disease including type 2 diabetes mellitus. This review examines epigenetic changes that occur with specific resistance exercises related to duration, intensity, and frequency and discuss possible mechanisms.