Antibiotics are pervasive contaminants in aqueous systems that pose an environmental threat to aquatic life and humans. Typically, antibiotics are developed to counteract bacterial infections; however, their prolonged and excessive use has provoked unintended consequences. The presence of excessive amounts of antibiotics and anti-inflammatory, anti-depressive, and contraceptive drugs in hospital and industrial wastewater poses a significant threat to the ecosystem, with groundwater containing drug concentrations of <1 mg/L to hundreds of µg/L. According to the literature, 33,000 people die directly from drug-resistant bacterial infections in Europe annually, which costs EUR 1.5 billion in health care and productivity loss. Consequently, the continuous spread of antibiotics in the ecosystem has led to greater interest in developing a sustainable method for effective antibiotic removal from wastewater. This critical review aims to present and discuss recent advances in the photocatalytic degradation of widely used drugs by ZnO-based nanostructures, namely (i) antibiotics; (ii) antidepressants; (iii) contraceptives; and (iv) anti-inflammatories. This study endows a comprehensive understanding of the degradation of antibiotics using ZnO-based nanomaterials (bare, doped, and composites) for effective treatment of wastewater containing antibiotics. In addition, the operational conditions and mechanisms involved during the photocatalytic degradation process are systematically discussed. Finally, particular emphasis is devoted to future challenges and the corresponding outlook with respect to toxic effects following the utilization of ZnO-based nanomaterials.