We have used both in situ radiation damage techniques and direct observations of ex-reactor materials to study radiation damage mechanisms in a range of zirconium-niobium (Zr-Nb) alloys with different initial microstructures. The aim has been to determine the relative stability of the different phases present under in-service conditions, including oxides and second phase particles (SPPs), and how damage to these phases alters the chemistry of the surrounding alloy matrix. A monoclinic-to-cubic transformation of the bulk oxide is observed by in situ ion irradiation experiments, followed by irradiation-induced grain growth. The possibility of radiation-induced stabilization of this cubic phase thus needs to be considered as an additional process that can occur in the regions of oxides exposed to high fluxes in service and may further affect the corrosion rates. In situ studies of β-Nb and Laves phase SPPs under ion irradiation showed that they behaved differently as a function of ion fluence and irradiation temperatures. The β-Nb SPPs show good stability under both ion and neutron irradiation to high damage levels and over a wide temperature range. The formation in flux, by a combination of irradiation-enhanced oxygen diffusion and the direct effects of radiation, of oxides that are both less well textured and with a more disrupted grain structure will also contribute to different corrosion rates in reactor. Finally, high-resolution energy-dispersive X-ray and atom probe tomography analysis were used to study changes to both SPP and matrix chemistry as result of radiation damage.