Viral diseases pose a major threat to fruit production worldwide, reducing productivity and fruit quality, and compromising the sustainability of crop systems. Unlike single infections, mixed infections of two or more viruses are recognized for their ability to intensify symptom severity, increase viral load, and exacerbate economic losses. This chapter provides an overview of the mechanisms underlying viral complexes in fruit crops. Special attention is given to the role of coinfections, whether simultaneous or sequential, and the impact of subviral agents, such as satellites and viroids, which can potentiate or attenuate disease expression. Examples from different fruit crops illustrate how viral complexes influence epidemiology and management, highlighting cases where resistance breakdown occurs in mixed infections. The emergence of new viral complexes, often associated with climate change and global trade, highlights the dynamic nature of these pathosystems. Current advances in biotechnology, including RNA interference (RNAi), genome editing (CRISPR-Cas), and the development of transgenic plants, are promising strategies for mitigating the challenges posed by complex infections. In addition to these approaches, integrating traditional methods, such as virus-free planting material, certification programs, and vector management, is also necessary. In conclusion, this chapter emphasizes the need for multidisciplinary approaches that combine virology, entomology, plant breeding, and bioinformatics. This integration is crucial for developing sustainable management strategies, ensuring long-term disease control and preserving fruit production in a global agricultural landscape.