Historically, adjuvant radiotherapy for early-stage breast cancer has included treatment of the entire breast. Breast conservation therapy (BCT), which employs whole-breast radiotherapy following lumpectomy, requires daily treatment for 5–7 weeks. The length of this treatment course proves difficult for some patients. In response, accelerated partial breast irradiation (APBI) has been investigated as a possible alternative to conventional post-lumpectomy treatment. This approach not only challenges the conventional treatment paradigm of whole-breast radiotherapy by reducing the treated volume, but also intensifies the dose delivered. By limiting the volume of breast tissue treated, the radiation dose delivery can be safely accelerated and the treatment time reduced to 5 days. In the United States, APBI has been most commonly delivered via brachytherapy (by either a multi-catheter implant or Mammosite balloon device) or by three-dimensional conformal radiotherapy (3D-CRT). One of the first techniques developed for APBI was multi-catheter interstitial brachytherapy. This article reviews completed trials of ABPI using the multi-catheter approach, as well as patient selection, placement technique, and dosimetric evaluation.