Leptospirosis has recently been recognized as another re-emerging infectious disease, both as epidemic in developing countries (Nicaragua, India) and as endemic in industrialized countries (USA). Molecular techniques have been successfully used for speciation, but have not replaced the gold standard serological techniques far identifying leptospires to the serovar level. Polymerase chain reaction is becoming the ideal diagnostic test, because leptospiral DNA can be detected both on the initial presentation of clinical illness and even months later, and results are rapidly available. Modern techniques of cellular and molecular biology are beginning to unravel the pathogenesis and pathophysiology of leptospirosis. Treatment continues to rely on penicillins and tetracyclines, but morbidity and mortality should decline as improvements in rapid diagnostic techniques become widely adopted and the disease becomes more widely recognized.