We study general aspects of NS5-brane instantons in relation to the stabilization of the volume modulus in Calabi-Yau compactifications of type II strings with fluxes, and their orientifold versions. These instantons correct the Kähler potential and generically yield significant contributions to the scalar potential at intermediate values of string coupling constant and volume. Under suitable conditions they yield uplifting terms that allow for meta-stable de Sitter vacua.1 The situation might seem to look better in type IIA theories, since there one can stabilize the Kähler moduli directly at the classical level by switching on fluxes [11]. However, the Kähler moduli are fixed again by solving a set of quadratic equations involving the triple intersection numbers, see equation (4.36) in [11]. So to find large values for the total volume, one ends up with similar difficulties as in type IIB.2 In N = 2 compactifications of type IIB, one also expect D5-brane instantons to contribute. However, after orientifold projection with O3/O7 planes, the D5 brane is not BPS and therefore harder to analyze. Furthermore, we look for a mechanism that also applies to IIA and heterotic string theories.