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Hydrangea macrophylla, commonly known as bigleaf, garden, French, or florist hydrangea, is the most economically important member of the Hydrangea genus, with a breeding history spanning hundreds of years. Bigleaf hydrangea breeding improvement has largely focused on aesthetic traits and there are few varieties tolerant or resistant to major diseases such as powdery mildew. Powdery mildew is an obligate biotrophic Ascomycete in the order Erysiphales represented by approximately 900 species worldwide. The disease-causing agent in hydrangeas is Golovinomyces orontii (formerly Erysiphe polygoni DC), which tarnishes the beauty, growth, and salability of bigleaf hydrangea plants, especially those packed closely in production environments. Chemical or biological control is commonly used in production. A recently published haplotype-resolved genome of bigleaf hydrangea enables targeted analyses and breeding techniques for powdery mildew resistance. Analyzing transcriptomes of tolerant and susceptible hydrangeas through RNA sequencing will lead to the identification of differentially expressed genes and/or pathways. Concurrent application of marker-assisted selection, genetic transformation, and gene editing will contribute to the development of powdery-mildew-resistant varieties of bigleaf hydrangea. The aim of this review is to give a general overview of powdery mildew, its impact on bigleaf hydrangea, current control methods, molecular mechanisms, and breeding prospects for powdery mildew resistance in bigleaf hydrangea.