Antidepressants such as amitryptiline and fluoxetine are on the list of modern essential medicines of the World Health Organization. However, there are growing concerns regarding the ecological impact of these pharmaceuticals, leading to a great need to improve current wastewater treatment procedures. In this contribution, we will report on the use of molecularly imprinted polymers (MIPs) for the extraction of antidepressants in water samples. MIPs were developed for fluoxetine and duloxetine, antidepressants belonging to the class of selective serotonin reuptake inhibitors (SSRIs). The binding capacity of these microparticles was evaluated using ultraviolet–visible (UV–Vis) spectroscopy. A new high-performance liquid chromatography (HPLC) procedure coupled to UV detection was developed, which enabled the study of mixtures of fluoxetine and duloxetine with other nitrogen-containing compounds. These results indicate that it is possible to selectively extract SSRIs from complex samples. Therefore, these versatile polymers are a promising analytical tool for the clean-up of water samples, which will benefit aquatic life and reduce the ecological impact of pharmaceuticals.