Chemical’s persistence is known to be an important parameter applied for decades to identify persistent organic pollutants in hazard and/or risk assessments. Nevertheless it is greatly challenged in the case of emerging contaminants such as pharmaceuticals because the persistence of these chemicals could be more affected by environmental conditions. This fact brings more challenges to the current system for evaluating the persistence of chemical contaminants. In this paper, challenges in assessing the persistence of pharmaceuticals were identified, and more importantly research needs were addressed based on the existing data and knowledge.