Abstract The twentieth anniversary issue of Comprehensive Psychiatry spans a period in the history of psychiatry that is undisputedly the era of psychopharmacology. Although it is commonly believed that this era was initiated with the advent of chlorpromazine in the early 1950s, a revisionist's version of history would probably credit Cade1 who reasoned his way from lethargy in guinea pigs to the control of manic excitement via lithium. Acknowledgment of the impact and applications of this discovery grew very slowly, and it was not until the mid 1960s that the importance of lithium in psychiatry gained wide recognition. Two volumes2,3 dealing comprehensively with the role of lithium in research and treatment were published in the 1970s. It has only been relatively recently that mania has emerged as a distinct entity worthy of independent study; an entire volume devoted exclusively to mania edited by Shopsin,4 was published in 1979. During the past two decades, several major scientific advances have contributed to our understanding of mania, including: (1) the advent of psychotherapeutic agents; (2) a renaissance of interest in psychopathology and diagnosis; (3) emphasis on biological and genetic etiologic factors; and (4) the growth of psychiatric epidemiology.