Due to outstanding scientific and technological progresses, the number of genetic tests is growing exponentially in clinical laboratories, supported by relatively inexpensive, fast, reliable, high-throughput techniques. It is unquestionable that genetic testing has helped to identify the molecular bases of monogenic disorders as well as a variety of genes involved in most mul-tifactorial pathologies. This in turn has allowed for personalized treatments and pharmacological therapies. However, it has also produced a paradox in the managed care of patients, in that genetic testing is now often perceived as a panacea, with assumptions that each single genetic polymorphism is associated with a specific, individual phenotype and/or clinical picture. Unfortunately, several processes regulating protein expression are still unknown, and their biological background has not been definitely recognized, so that the link between the genotype, the phenotype and the clinics is not always obvious, and it is often even more challenging to address how much the link between genes and environment will impact on the managed care of the patients. The present article aims to critically review the complex and multifaceted relationship linking genes, biochemistry and clinics, highlighting advantages and drawbacks of genetic testing in monogenic disorders, po-lygenic pathology and in the prediction of the pharmacological response.