Background: Valproic acid is an important anticonvulsant and mood-stabilizing drug. It is also used in the therapy of bipolar disorders, migraine, cancer and neurodegenerative disorders. The use of valproate in epileptic disorders depends on trial and error with fluctuation of the prescribed dose until the patient is controlled with the least effective dose without side effects. With the emergence of pharmacogenomics, it is important to know the genes regulating valproic acid signaling pathways, related transporters, receptor mutations, pharmacokinetics, pharmacodynamics and adverse drug reactions. Thereafter, we can use valproic acid with more efficacy and tolerability. Highlight the genetic variations associated with valproic acid mechanism of action, pharmacokinetics, pharmacodynamics and side effects.We have searched literatures in PubMed, google scholar,Egyptian bank of knowledge and science direct. Conclusion: There are several candidate genes affecting valproic acid efficacy, tolerability and safety. Therefore, we can prescribe the right valproic dose to the right patient at the right time, thus, allowing optimization of valproic acid therapy.