Cystic fibrosis (CF) presents with various symptoms that impair day-to-day functioning and require lifelong treatment. Due to the chronic and severe nature of this disease, families are often impacted by the stress associated with treatment, complications of the disease, and the understanding that their loved one will one day die from CF. This article seeks to address a perceived gap in the literature for providing a model-specific approach to address psychosocial stress in families affected by CF. We provide a rationale for using solution-focused brief therapy (SFBT) to work with this population based on its empirically supported effectiveness, versatility, and capacity to be brief in nature. We describe how SFBT interventions can be used by practitioners working with this population, present a fictitious case illustration depicting the clinical use of specific SFBT interventions, and offer suggestions for future research. (PsycInfo Database Record (c) 2021 APA, all rights reserved).