We describe how the amorphous fluoropolymer CYTOP can be advantageously used as a waveguide cladding material in integrated optical circuits suitable for applications in integrated biophotonics. The unique refractive index of CYTOP (n = 1.34) enables the cladding material to be well index-matched to an optically probed sample solution. Furthermore, ultra-high index contrast waveguides can be fabricated, using conventional optical polymers as waveguide core materials, offering a route to large-scale integration of optical functions on a single chip. We discuss applications of this platform to evanescent-wave excitation fluorescence microscopy, passive and/or thermo-electrically-controlled on-chip light manipulation, on-chip light generation, and direct integration with microfluidic circuits through low-temperature bonding.