Originally thought of as "junk RNA", long non-coding RNA (lncRNA) has been shown over the last decade to play active regulatory roles in many vital cellular processes. The accepted primary mechanism of lncRNA regulatory activity is through chromatin remodeling and methylation of the genome, while there are also recent data to suggest additional mechanisms, such as altered RNA processing and enhancer activity. Aberrant expression of lncRNA has been linked with various disease processes, including cancer. One of the most well studied lncRNA, Hox Transcript Antisense Intergenic RNA (HO-TAIR), is one such lncRNA whose enhanced expression has been associated with carcinomas of the breast. In addition to reviewing the extensive research focused on HOTAIR expression and regulation of breast cancer through canonical pathways, we will examine new studies that suggest the ability of HOTAIR to regulate microRNA (another type of non-coding RNA) through direct binding inhibition, and how dysregulation of HOTAIR expression is relevant to breast cancer.