A prodrome is a premonitory set of signs and symptoms indicating the onset of a disease. Prodromes are frequently reported by hereditary angioedema (HAE) patients, antedating attacks by a few hours or even longer. In some studies, high incidence of prodromes was reported by patients, with considerable number being able to predict oncoming attacks. Regrettably, prodromes have never received a consensual definition and have not been properly investigated in a systematic fashion. Therefore, their nature remains elusive and their contribution to the diagnosis and treatment of disorders is uncertain. The term “prodrome,” as used in various pathologies, denotes different meanings, timing, and duration, so it may not be equally suitable for all clinical situations. Perception of a prodrome is unique for each individual patient depending on self-experience. As modern drugs delegate the administration decision to the patients, early detection of a developing attack may help mitigate its severity and allow deployment of appropriate therapy. New diagnostic instruments were recently developed that can assist in defining the attributes of prodromes and their association with attacks. We will review the prodrome phenomenon as exhibited in certain clinical situations, with an emphasis on prodromes of HAE.