This chapter discusses nucleation involving vacancy migration of clusters and bubbles of helium in metals. At high temperatures and low helium production rates, a helium-vacancy cluster absorbs sufficient thermal or irradiation-induced vacancies to keep the internal pressure close to its equilibrium value. Helium precipitation is controlled by thermally activated nucleation processes involving two mobile components (helium atoms and vacancies). The nucleation barrier Gc depends strongly on the helium concentration (supersaturation) and on the nucleation site. The development of the bubble population depends not only on the intrinsic parameters of the material (solubility, diffusivity, sink structure, etc.) and external parameters (temperature, helium and displacement production rate, etc.) but also upon the way on which the experiment is conducted. The temperature dependence of final bubble density is determined by the dissociation energy of helium atoms from bubble nuclei. The predictions of the theory can be compared with experimental data obtained from TEM observation of the bubble structure after high temperature α-implantation into stainless steels. The investigated materials have a very complex defect structure which leads to rather heterogeneous bubble distributions. The theory has been extended to bubble nucleation on dislocations, precipitate-matrix interfaces and particularly on grain boundaries.