A work group from the American Physical Therapy Association (APTA) Academy of Oncologic Physical Therapy developed a clinical practice guideline to aid clinicians in identifying interventions for people with breast cancer-related lymphedema, targeting volume reduction, beginning at breast cancer diagnosis and continuing through cancer treatments and survivorship. Following a systematic review of published studies and a structured appraisal process, recommendations were developed to guide physical therapists and other health care clinicians in their intervention selection. Overall, clinical practice recommendations were formulated based on the evidence for each intervention and were assigned a grade based on the strength of the evidence. The evidence for each specific intervention was synthesized and appraised by lymphedema stage, when the information was available. In an effort to make recommendations clinically applicable, they were presented by modality throughout the care trajectory. Methodology and research populations varied significantly across studies, and it will be important for future research to use standardized definitions for participant characteristics, diagnostic criteria, and interventions.