Antibody variable domains vary widely in their intrinsic thermodynamic stability. Despite the mutual stabilization of the domains in the scFv fragment, most scFv derived from monoclonal antibodies without further engineering show poor to moderate stability. The situation gets more complex for Fab fragments and full-sized antibodies: while the disulfide-linked C(L)/C(H) heterodimer shows very limited thermodynamic stability, its unfolding kinetics are very slow. The same is true for Fab fragments, which, due to this kinetic stabilization, appear to be more stable than their thermodynamic stability suggests. However, suboptimal variable domains can be engineered for improved stability and folding efficiency while preserving their antigen-binding specificity and affinity, either by a limited number of point mutations or by grafting their antigen specificity to superior variable domain frameworks.