This chapter describes thermal and light-induced conformational changes experienced by small compounds in cryogenic matrices. For thermally induced processes, changing the temperature of the cold substrate during matrix deposition and annealing of the deposited matrix are useful methods to change the relative populations of the conformers. In the case of light-induced conformational changes, the use of both UV–visible and IR excitations is described, for the latter with focus on processes promoted by narrowband light. Time-dependent experiments and computations on the conformational change of HONO are described providing a prototype system for dynamical studies of conformational changes in matrix-isolated species.