Intrinsic or acquired resistance to commonly used therapeutic agents is a major challenge in treating cancer patients. Decades of research have unraveled several unique and common mechanisms that could contribute to drug resistance in breast cancer. Recent studies unraveled the regulatory role of small noncoding RNA, designated as microRNA (miRNA), that were thought to be "junk" RNA in the past. Practically all aspects of cell physiology under normal and disease conditions were found to be regulated by miRNAs. In this review, we will discuss how miRNA profile is altered upon resistance development and the critical regulatory role miRNAs play in conferring resistance to commonly used therapeutic agents. It is hoped that further studies will lead to use of these differentially expressed miRNAs as prognostic and predictive markers, as well as novel therapeutic targets to overcome resistance.