The cardiovascular toxicity of drugs constitutes an important area of attention for clinicians, drug developers and general population. Numerous medications currently used to treat severe health issues like cancer, diabetes, AIDS and mental illness, have severe limitations due to mild to severe cardiac complications, directly attributable to the treatment. Some of these side effects disappear when the treatment is stopped. However, in other cases, cardiotoxic symptoms begin to appear much later. Susceptibility to cardiotoxic drugs is highly influenced by pre-existing conditions but during the last decades genetic and geographic studies have shown that genetic polymorphisms or ethnic background play significant predictive or prognostic roles in cardiovascular toxicity. The aim of this chapter is to summarize some examples that illustrate the predisposing role of genetic and epigenetic factors in increasing the pathogenesis of drug-induced cardiovascular toxicity.