We review recent progress in determining the effects of D-brane instantons in N=1 supersymmetric compactifications of Type II string theory to four dimensions. We describe the abstract D-brane instanton calculus for holomorphic couplings such as the superpotential, the gauge kinetic function and higher fermionic F-terms. This includes a discussion of multi-instanton effects and the implications of background fluxes for the instanton sector. Our presentation also highlights, but is not restricted to the computation of D-brane instanton effects in quiver gauge theories on D-branes at singularities. We then summarize the concrete consequences of stringy D-brane instantons for the construction of semi-realistic models of particle physics or SUSY-breaking in compact and non-compact geometries.