This chapter reviews the role of the extracellular matrix (ECM) in fungal biofilm resistance, particularly in Candida species, Cryptococcus neoformans, and Aspergillus fumigatus. ECM serves as a protective barrier that contributes to biofilm resistance to both host immune defenses and antifungal drug treatment. In Candida biofilms, the ECM is involved in drug sequestration and limits the efficacy of antifungal agents across multiple layers. Previous studies of matrix composition in Candida revealed critical components such as mannan-glucan complexes that protect against drug penetration. Similarly, ECMs in C. neoformans and A. fumigatus contribute to biofilm integrity and drug resistance with specific matrix elements like glucuronoxylomannan in C. neoformans and galactosaminogalactan in A. fumigatus. The chapter highlights matrix-mediated drug resistance mechanisms including the sequestration of antifungal drugs and modulation of host immune responses. It suggests that targeting ECM components could offer new avenues for biofilm-related infection therapies.