As a modification in the application of local anesthesia for high-risk patients, adjustments to the group or type of anesthetic, dosage, or vasoconstrictor type may be necessary, or the procedure may need to be postponed. For cardiovascular patients, the use of adrenaline as a vasoconstrictor is justified at dilutions of 1:100,000 or 1:200,000. The maximum allowable dose of adrenaline is 0.4 mg for adults. An alternative to adrenaline is the use of prilocaine with felypressin. Aspiration is always necessary for all cardiovascular patients. Patients with kidney failure do not require a lidocaine dose adjustment. Articaine is currently the local anesthetic of choice for chronic kidney disease in dental treatment. Patients on dialysis and those suffering from chronic glomerulonephritis and pyelonephritis represent a relative contraindication for anesthetic use. For patients with liver disease, it is recommended to apply the lowest effective dose of anesthetic. One option is to use ester group local anesthetics. Most diabetic patients should tolerate a local anesthetic with 1:100,000 epinephrine well. In cases of uncontrolled diabetes, the recommendation is to limit adrenaline to 0.04 mg and levonordefrin to 0.2 mg. Regarding pregnant women, current data indicate that articaine, lidocaine, and mepivacaine are safe for use without endangering the fetus. On the other hand, prilocaine may induce methemoglobinemia in the fetus and is therefore avoided. If a dental procedure is necessary during pregnancy, it is best to perform it during the second trimester using a maximum of 4-6 mL of local anesthetic. Elective dental treatments in patients with hyperthyroidism are postponed until the thyroid condition is balanced. If a vasoconstrictor is necessary, the recommendation is felypressin. Considering all of the above, it is evident that understanding local anesthetics and their specificities for use in certain patient groups is of great importance.