This review summarizes gender differences (GDs) in drug response. Although GDs have been described both in pharmacodynamics and pharmacokinetics, their role in clinical practice is not yet completely elucidated. The evidence that women have been less enrolled in clinical trials and that a gender-specific analysis usually is not included in the evaluation of results, contributes largely to this uncertainty. Consequently, adverse drug reactions (ADRs) are still higher in females than in males. Since sex is a fundamental biological variable that cannot be discounted, GDs in pharmacology have to be considered in order to improve drug safety efficacy and to optimize medical therapy both in men and women.