Plague has caused ravaging outbreaks, including the Justinian plague and the “black death” in the Middle Ages. The causative agents of these outbreaks have been confirmed using modern molecular tests. The vector of plague during pandemics remains the subject of controversy. Nowadays, plague must be suspected in all areas where plague is endemic in rodents when patients present with adenitis or with pneumonia with a bloody expectorate. Diagnosis is more difficult in the situation of the reemergence of plague, as in Algeria for example, told by the first physician involved in that outbreak (NM). When in doubt, it is preferable to prescribe treatment with doxycycline while waiting for the test results because of the risk of fatality in individuals with plague. The typical bubo is a type of adenitis that is painful, red and nonfluctuating. The diagnosis is simple when microbiological analysis is conducted. Plague is a likely diagnosis when one sees gram-negative bacilli in lymph node aspirate or biopsy samples. Yersinia pestis grows very easily in blood cultures and is easy to identify by biochemical tests and MALDI-TOF mass spectrometry. Pneumonic plague and septicemic plague without adenitis are difficult to diagnose, and these diagnoses are often made by chance or retrospectively when cases are not part of an epidemic or related to another specific epidemiologic context. The treatment of plague must be based on gentamicin or doxycycline. Treatment with one of these antibiotics must be started as soon as plague is suspected. Analysis of past plague epidemics by using modern laboratory tools illustrated the value of epidemic buboes for the clinical diagnosis of plague; and brought new concepts regarding its transmission by human ectoparasites.