Plant production systems worldwide are struggling to meet the diverse and increasing needs of humankind while also facing challenges such as climate change and biodiversity loss. This, combined with the desirable transition from the use of conventional pesticides to more sustainable plant protection solutions, has led to an urgent, and increasing, need for low-risk plant protection products (PPPs) to be developed, applied, and integrated into management practices across all types of plant production systems. Despite a high demand from end users and consumers together with joint political goals at the EU level to replace conventional pesticides, the number of low-risk PPPs on the European market remains low, in comparison to synthetic agrochemicals. In this review, we summarize knowledge about the policy, technical, and administrative issues hampering the process of bringing new low-risk PPPs to the European market. We present an overview of the challenges in using the low-risk PPPs that are currently available within the EU agricultural, horticultural, and forestry sectors. We describe the variation in modes of action and the limitations associated with different application techniques and give concrete examples of problems and solutions from Swedish plant production sectors, in contrast to global perspectives as demonstrated by examples from African agriculture. Finally, we conclude that trans-sectoral, multi-actor approaches are required and provide suggestions on how to address the remaining knowledge gaps related to efficiency, application, and economics of low-risk PPP use in Integrated Pest Management (IPM) solutions for plant protection to improve future food security in Europe.