We establish a reduction principle to derive Li–Yau inequalities for non-local diffusion problems in a very general framework, which covers both the discrete and continuous setting. Our approach is not based on curvature-dimension inequalities but on heat kernel representations of the solutions and consists in reducing the problem to the heat kernel. As an important application we solve a long-standing open problem by obtaining a Li–Yau inequality for positive solutions u to the fractional (in space) heat equation of the form (-Delta )^{beta /2}(log u)le C/t, where beta in (0,2). We also show that this Li–Yau inequality allows to derive a Harnack inequality. We further illustrate our general result with an example in the discrete setting by proving a sharp Li–Yau inequality for diffusion on a complete graph.