Photonic crystal fibers (PCFs), also known as microstructured optical fibers, are a highlighted invention of optical fiber technology which have unveiled a new domain of manipulating light in engineered fiber waveguides with unparalleled flexibility and controllability. Since the report of the first fabricated PCF in 1996, research in PCFs has resulted in numerous explorations, development and commercialization of PCF-based technologies and applications. PCFs contain axially aligned air channels which provide a large degree of freedom in design to achieve a variety of peculiar properties; numerous PCF-based sensors have been proposed, developed and demonstrated for a broad range of sensing applications. In this chapter, we will review the field of research on design, development and experimental achievement of PCF-based interferometric sensors for physical and biomedical sensing applications.