Epithelial cells and most adherent normal cells rely on adhesion-dependent, integrin-mediated survival signals from the extracellular matrix (ECM) to survive. When these cells are deprived of adhesion to the ECM, they undergo a specific form of apoptosis termed “anoikis.” In contrast, malignant cells have attained mechanisms to enable them to survive in the absence of adhesion. This acquisition of anoikis resistance allows tumor cells to grow in an anchorage-independent manner and achieve metastatic disease. Recent studies have identified the mitochondrial Bcl2-inhibitor of transcription (Bit1) protein as part of a novel anoikis pathway. This review will focus on the biological function of Bit1 in the anoikis process, the underlying molecular mechanism of Bit1 apoptotic function, and its role in tumor metastasis.