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In a clinical practice guideline published in Practical Radiation Oncology, the American Society for Radiation Oncology presented recommendations to inform best clinical practices on using partial breast irradiation (PBI). Simona F. Shaitelman, MD, and colleagues convened a task force to address four questions related to appropriate indications and techniques for PBI as an alternative to whole breast irradiation (WBI). The team developed guidelines based on a systematic review and created recommendations using a predefined consensus-building methodology. PBI is strongly recommended for patients with early-stage invasive breast cancer with grade 1 to 2 disease, estrogen receptor-positive histology, aged 40 or older, and tumor size 2 cm or less. Clinicians used three-dimensional conformal radiation therapy, intensity-modulated radiation therapy, multicatheter brachytherapy, and single-entry brachytherapy to deliver PBI results in similar ipsilateral breast recurrence (IBR) as WBI with long-term follow-up. Due to an underrepresentation of certain patient characteristics and tumor features in randomized controlled trials, the IBR risk for patients with these features could not be fully defined.