Biomarkers are defined as characteristics (e.g., proteins, RNA, single nucleotide polymorphisms, imaging) that are objectively measured and evaluated as indicators of pathogenic processes or pharmacologic responses to therapeutic intervention. Biomarkers are important in clinical trials where the robust biomarker reflects the underlying disease process in a sensitive and reliable manner. For myasthenia gravis (MG), acetylcholine receptor and muscle-specific kinase antibodies, as well as single-fiber electromyography, serve as excellent biomarkers for diagnosis but do not adequately substitute for clinical evaluations to predict treatment response. New technologies are emerging that enable broad biomarker discovery in biological fluids. Biomarker evaluation is ideally done in the context of longitudinal clinical trials. The MGTX trial has collected plasma and serum for RNA and protein analysis and thymus, which will allow robust biomarker discovery. The ultimate goal will be to identify candidates for a reliable substitute for a clinically meaningful end point that is a direct measure of the effectiveness of a therapy in the context of a continuum of disease natural history and a patient's overall well-being. © 2012 New York Academy of Sciences.