Cholesterol-lowering statin drugs are among the most frequently prescribed for reducing human blood cholesterol and they have been detected as contaminants in natural waters. In this study the photochemical behavior of atorvastatin (lipitor) was investigated at two different concentrations of 35.8 μM (20 mg L−1) and 35.8 nM (20 μg L−1) using a solar simulator and a UV reactor. Photochemical fate in natural waters can be described in most cases by the sum of the loss due to hydrolysis, direct photolysis, and, reaction with hydroxyl radical (OH), singlet oxygen (1O2) (or O2 (1D)), and excited state dissolved organic matter (DOM). The absolute bimolecular reaction rate constant with OH was measured, using pulsed radiolysis, (1.19 ± 0.04) × 1010 M−1 s−1. The reaction rate constant of 1O2 was determined to be (3.1 ± 0.2) × 108 M−1 s−1. Under the experimental conditions used, at high atorvastatin concentration (35.8 μM) the contribution of singlet oxygen (1O2) to the photodegradation of atorvastatin in natural waters was higher than that of hydroxyl radical, and accounted for up to 23% of the loss in aqueous solutions. Whereas, at a concentration of 35.8 nM, 1O2 (and OH) both played a minor role in the removal of this compound. Lastly, it also appears that atorvastatin reacts with 3DOM* contributing to its loss in simulated natural waters.