In recent years pharmacogenomic research has highlighted several genetic biomarkers of treatment toxicity and efficacy, dealing with drug metabolism, transport and mechanism of action. More recently, polymorphisms in miRNA encoding genes, their targets or factors involved in their maturation are rising as new pharmacogenomic markers in cancer. miRNAs are brief ncRNAs involved in DNA translational control, with an effect on mRNA and protein-expression levels. The study of genetic polymorphisms in genes involved in miRNA translational control machinery could give innovative insights in pharmacogenomics. This review summarizes the most recent and promising results in the field and gives an overview of the future perspective of personalized cancer therapy.