Fibromyalgia (FM) is a serious and debilitating condition, encompassing a wide range of symptoms. Physical therapists often advocate the incorporation of leisure time physical activity (exercise training or recreational physical activity) as an important management strategy for individuals with FM. Decisions about physical activity prescription in clinical practice are informed by a variety of sources. This topical review considers physical activity prescription using the E-Model as a framework for best practice decision making. We examine findings from randomized trials, published experts, and qualitative studies through the lens of the model's five Es: 1) evidence, 2) expectations, 3) environment, 4) ethics, and 5) experience. This approach provides a robust foundation from which to make best practice decisions. Application of this model also facilitates the identification of gaps and discrepancies in the literature, future opportunities for knowledge exchange and translation, and future research.