Pluripotent stem cells, such as embryonic stem cells and induced pluripotent stem cells, are an important tool in the studies focusing at the differentiation of various cell types, including skeletal myoblasts. They are also considered as a source of the cells that due to their pluripotent character and availability could be turned into any required tissue and then used in future in regenerative medicine. However, the methods of the derivation of some of cell types from pluripotent cells still need to be perfected. This chapter summarizes the history and current advancements in the derivation and testing of pluripotent stem cells-derived skeletal myoblasts. It focuses at the in vitro methods allowing the differentiation of stem cells grown in monolayer or propagated as embryoid bodies, and also at in vivo tests allowing the verification of the functionality of obtained skeletal myoblasts.