<p>Quaking (QKI), a member of the signal transduction and activators of RNA (STAR) family of RNA-binding proteins, affects a wide range of functions, including alternative splicing, mRNA precursor processing, mRNA transport and localization, mRNA stabilization, and translation. Recently, QKI has been found to have critical roles in vasculogenesis and angiogenesis due to its effects on alternate splicing and other post-transcriptional modifications involving small RNAs in the endothelial cells (ECs). Aberrant expression or mutation of QKI in ECs can result in pro- or anti-angiogenic effects under different physiological and pathological conditions, including tumor angiogenesis. However, the regulatory roles of QKI in EC biology remain poorly described. This review summarizes our current understanding of the QKI isoforms and their functions in ECs, as well as the potential utility of QKI as an emerging translational target for angiogenic-based therapies.</p>