Breast cancer is the most ubiquitous type of neoplasms among women worldwide. Molecular aberrations associated with breast development and progressions have been extensively investigated in recent years. An AMP-activated kinase (AMPK) initially identified as a cellular energy sensor that plays a crucial role in cellular energy homeostasis. Intensive research over the last decade about the molecular mechanisms of AMPK has demonstrated that AMPK mediated diverse biological functions are achieved through phosphorylation and regulation of multiple downstream signaling molecules in normal tissue. Downregulation of AMPK activity or decreased level involved in the promotion of breast tumorigenesis, and thus activation of AMPK found to oppose tumor progression. In this review, we epitomize the recent advances in exploring the tumor suppressor function of AMPK pathways. Besides, we discuss the developments in the area of AMPK activator and its molecular mechanisms for breast cancer treatment.