The concept of pharmacogenetics (PGx), first described more than six decades ago, involves the use of an individual’s genetic information to predict response to drug, thus affecting both efficacy and toxicity. In the last decade, pharmacogenetics guidelines by the Clinical Pharmacogenetics Implementation Consortium (CPIC) and Dutch Pharmacogenetics Working Group (DPWG) were developed for the clinicians and health-care professionals to guide drug selection, predict therapeutic outcomes, and prevent drug-induced adverse events. The US Food and Drug Administration (FDA), the European Medicines Agency etc, also provides drug label information that provides information of pharmacogenetic biomarkers relevant to specific drugs. These initiatives have led to successful translation of pharmacogenetic information into routine clinical practice such as TPMT, NUDT15 variant for predicting thiopurine toxicity, CPY2C19 genotyping for guiding clopidogrel therapy, CYP2D6 for tamoxifen therapy etc. However, despite various PGx guidelines and substantial progress achieved using pharmacogenetics information in clinical practice, there are many challenges that still remain and which pose a big hurdle in the widespread implementation of genome guided precision medicine. These challenges include, but not limited to, lack of information on rare genetic variation, under-representation of diverse populations data, lack of evidence of the clinical utility, so on and so forth. Addressing all the challenges and finding solutions will be of utmost importance in order to reduce adverse drug events, and have a patient-specific precision medicine.