We develop a theory of universal central extensions of Hom-Lie algebras. Classical results of universal central extensions of Lie algebras cannot be completely extended to Hom-Lie algebras setting, because of the composition of two central extensions is not central. This fact leads to introduce the notion of universal α-central extension. Classical results as the existence of a universal central extension of a perfect Hom-Lie algebra remains true, but others as the central extensions of the middle term of a universal central extension is split only holds for α-central extensions. A homological characterization of universal (α)- central extensions is given.