Amlodipine and olmesartan are two different antihypertensive drugs used in combination in the management of mild to severe hypertension. Degradation of the drug is one of the fatal processes. The potency and efficiency decrease in the presence of degradation products. The univariate spectrophotometric methods cannot provide adequate information for assessment of the presence of the degradation products. In this paper, three different multivariate models were utilized for the assessment of amlodipine and olmesartan in the presence of their degradation products. These methods are principal component regression (PCR), partial least square (PLS), and classical least square (CLS). The linearity range of these methods were 2-10 µg/ml  for both drugs. The limits of detection of these methods were from 0.466 to 0.637 µg/ml for amlodipine, and from 0.435 to 0.561 µg/ml for olmesartan while the limits of quantification were from 1.413 to 1.931 µg/ml for amlodipine, and from 1.318 to 1.709 µg/ml for olmesartan.