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Phenylketonuria is a rare inborn error of amino acid metabolism presenting with autosomal recessive pattern. In the majority of cases, PKU is caused by mutations in the phenylalanine hydroxylase gene (PAH), which catalyses the essential hydroxylation of phenylalanine (Phe) to tyrosine (Tyr) in the presence of its natural cofactor - tetrahydrobiopterin (BH4). In this paper we review the recent knowledge of molecular genetics of PKU, trends in research and we also discuss the molecular diagnostic approaches in this disease. Intensive research has been conducted in the last decade in order to determine the relationship between patients' genotype and clinical picture of the patient, as well as to most accurately assign the relationship of genotype and patients' responsiveness to tetrahydrobiopterin treatment. In this article we review the recent knowledge of genotype-phenotype correlations and we discuss possible causes of inconsistencies observed in many studies. In addition, we cite the latest findings regarding personalized therapy in PKU regarding cofactor treatment and we also discuss the limitations of genotype-based predictions of BH4 responsiveness. Besides, we bring up the latest data from molecular-genetic studies in Slovakia as well as the spectrum of most frequent mutations and genotypes identified in the Slovak population. This data could be useful for all clinical workplaces in Slovakia. [ABSTRACT FROM AUTHOR]