(1) Background: This study was planned to assess the concentration of antihypertensive drugs (AHD) in the blood serum in patients with controlled and uncontrolled arterial hypertension (AH). (2) Methods: We assessed 46 patients with AH. Based on the results of 24 h blood pressure monitoring (ABPM), the patients were randomized into two groups. The first group consisted of the patients with controlled AH; the second group consisted of the patients with uncontrolled AH. Venous blood was taken in both groups of patients in the morning before and 2 h after taking drugs to assess the concentration of lisinopril, amlodipine, valsartan, and indapamide. (3) Results. The first group included 27 patients, and the second group 19 patients. In patients with uncontrolled AH, the median concentrations of lisinopril, indapamide, amlodipine, and valsartan before and after taking the drugs did not differ from patients who reached the target BP values. (p> 0.05). In some patients with uncontrolled and controlled (shown for the first time) AH the concentration of AHD was below the limit of quantitative determination. (4) Conclusions. The obtained results indicate that the pharmacokinetics of AHD, apparently, does not play a significant role in the development of ineffectiveness of the ongoing therapy for AH. Therapeutic drug monitoring can be used to test adherence to the treatment.