The main aim of this work was to collect and present the polymorphisms that have been identified and tested and that may potentially have an influence on the effect of analgesic therapies. Opioid drugs are one of the most commonly used painkillers in the treatment of postoperative, neoplastic and post-traumatic pain. Opioid receptors and their types: μ, δ, κ, purinergic and adrenergic receptors contribute to nociceptive stimulation and their modulation. The analgesic effect induced by opioids is dependent on many factors, such as age, sex, body mass and the occurrence of different polymorphic variants of genes encoding opioid, purinergic and adrenergic receptors. Many polymorphisms have been identified within the following genes: OPRM, OPRK, OPRD, ADRB1 and P2RX7, encoding the following receptors: μ, κ, δ, purinergic P2X and β1-adrenergic. The most common polymorphism is the single nucleotide polymorphism (SNP-single nucleotide polymorphism). The occurrence of some polymorphic forms may generate differences in expression and have an impact on the physicochemical properties of receptors, which results in different levels of analgesia in the population and the generation of side effects. The relation between the occurrence of polymorphic variants of the genes of receptors participating in nociceptive stimulation and the increased or reduced demand for opioids necessary to achieve analgesia has been confirmed. Mechanisms in which polymorphisms affect the modification of the anesthetic response to opioids in most cases remain unknown. Further research on opioid, purinergic and adrenergic receptors polymorphisms may improve the effectiveness of opioid therapies by regulating the dose to the patient’s individual pain phenotype, and may reduce the risk of side effects resulting from using too high doses of the drug.