The influence of biological sex on pharmacokinetics and pharmacodynamics has been previously described for each step of the metabolic cascade of pharmaceuticals. Women and men display differences in distribution, metabolism, and excretion of drugs for several biologic reasons. Estrogens are relevant in these processes, but cannot be regarded as the only responsible mechanism. Sex differences in the incidence of adverse drug reactions and pharmacotoxicity have also been reported for several classes of drugs and specifically for several cardiovascular preparations. Given the high incidence of cardiovascular conditions and thus the broad use of these drugs in the general population, these reports have to be considered of relevance to public health. Nonetheless, increased knowledge has not translated into the development and implementation of gender-specific pharmacologic guidelines which appear as the only effective strategy to minimize the incidence of sex-specific side effects and adverse drug reactions. In the present review, we analyze the basic aspects of sex-specific pharmacodynamics and present several examples of gender dimorphism in cardiovascular drugs. We also suggest measures to analyze and possibly improve current therapeutic strategies.