Viral diseases cause persistent threats to fruit crop production worldwide, often causing severe yield losses, compromised fruit quality, and shortened orchard lifespans. Unlike bacterial or fungal pathogens, plant viruses lack effective curative treatments, making prevention through the use of healthy, virus-free planting materials the cornerstone of sustainable fruit crop management. This chapter examines the critical role of tissue culture technologies in the production and supply of virus-free planting materials for major fruit crops, including banana, citrus, apple, grapevine, and berries. The discussion covers the diverse spectrum of economically significant fruit viruses, their transmission routes, and their profound impact on productivity and industry sustainability. Detailed protocols and principles of plant tissue culture are described, with an emphasis on meristem-tip culture, thermotherapy, chemotherapy, cryotherapy, and advanced combined approaches for the effective elimination of viruses. The chapter highlights the importance of accurate virus detection and multi-stage indexing, integrating serological, molecular, and next-generation sequencing techniques. Certification systems, both national and international, are reviewed for their role in safeguarding the health of propagated materials from laboratory to nursery and ultimately to growers. The chapter concludes with practical recommendations for research, policy, and industry to enhance the effectiveness and accessibility of clean plant programs, supporting the global fruit industry’s resilience and long-term productivity in the face of evolving viral challenges.