The skeletal muscle is a complex tissue that represents most of the muscle tissue in mammals and plays a key role in health and in the body's function. It is a heterogeneous tissue whose contractile and metabolic functions depend on type, size, and quality of a large number of proteins. The multitude of proteins, the relationships that exist between them, and functional changes that occur in different muscle pathologies make their investigation to be challenged. In this chapter, current approaches in proteomic studies, its application, specific technical advice, and recent progress of the most important techniques based on antigen-antibody interactions used for the analysis of muscle proteins involved in different muscle diseases are presented.