The subject of the thesis is the study of operator functions in the setting of symmetric operator spaces. In this latter setting, it is of great importance to analyze the properties of so-called operator functions A --> f(A), where the variable A is a self-adjoint operator and f is a complex-valued Borel function on the real line. The thesis study the question of differentiability of this type of operator functions. The latter question is intimately related to the study of commutators. Text not only extends existing results to the setting of unbounded self-adjoint linear operators, but it is also shown that this can be obtained via a unified approach utilizing the left regular representation of von Neumann algebras.