Interindividual variability in response to drugs used in anesthesia has long been considered the rule, not the exception. It is important to mention that in anesthesiology, the variability in response to drugs is multifactorial, i.e., genetic and environmental factors interact with each other and thus affect the metabolism, efficacy, and side effects of drugs. Propofol (2,6-diisopropylphenol) is the most common intravenous anesthetic used in modern medicine. Individual differences in genetic factors [single nucleotide polymorphisms (SNPs)] in the genes encoding metabolic enzymes, molecular transporters, and molecular binding sites of propofol can be responsible for susceptibility to propofol effects. The objective of this review (through the analysis of published research) was to systematize the influence of gene polymorphisms on the pharmacokinetics and pharmacodynamics of propofol, to explain whether and to what extent the gene profile has an impact on variations observed in the clinical response to propofol, and to estimate the benefit of genotyping in anesthesiology. Despite the fact that there has been a considerable advance in this type of research in recent years, which has been largely limited to one or a group of genes, interindividual differences in propofol pharmacokinetics and pharmacodynamics may be best explained by the contribution of multiple pathways and need to be further investigated.