Ghrelin, a 28 amino acid gut brain peptide, acts as an endogenous ligand for its receptor, the growth hormone secretagogue receptor, to exercise a variety of functions ranging from stimulation of growth hormone secretion, regulation of appetite and energy metabolism, and cell protection to modulation of inflammation. This review summarizes the advance in the regulation of ghrelin expression and secretion. We introduce the structure of ghrelin promoter, the processing and modification of ghrelin precursor, and the regulation mechanism in these processes. Then we discuss factors found to be important in the regulation of ghrelin production, including nutrients, hormones, and autonomic nervous system. Finally, we outline the alteration in the level of ghrelin in certain physiological and pathological status.