This chapter provides a comprehensive analysis of the EU legal framework governing novel foods and pre-market authorization. By examining several examples of consultations regarding the novel food status of mushroom and mycelium-based products (MMPs), it explores the requirements for demonstrating a history of safe use. The chapter then focuses on the technical aspects involved in preparing a novel food application, with particular reference to the most recent guidance documents published by the European Food Safety Authority (EFSA). Furthermore, the chapter critically examines the Qualified Presumption of Safety (QPS) list and other mechanisms designed to streamline the risk assessment process for MMPs. It also highlights several challenges and gaps in toxicological data related to filamentous fungi, providing insights into the complexities of ensuring the safety of these products.