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Chromogranin A (CgA), which is an intrinsically disordered protein that belongs to the granin family, was first discovered in the bovine adrenal medulla, and later identified in various organs. Under certain physiological conditions, CgA is cleaved into functionally diverse peptides, such as vasostatin-1, pancreastatin, and catestatin. In this review, we first describe the historical and systematic challenges for elucidating the molecular structures of CgA and its derived peptides and give a perspective of utilizing emerging techniques through integrative approaches. Subsequently, we review specific biological processes associated with CgA and its derived peptides in the neuroendocrine, immune, and digestive systems. Finally, we discuss biomedical applications of CgA as a biomarker, suggesting future directions toward translational and precision medicine.