The intraspinal use of methylprednisolone acetate (Depo-Medrol, Upjohn Company, Kalamazoo MI) began in 1960, followed 10 years later by reports of complications. In 1960, methylprednisolone acetate was first injected by the epidural route to treat low-back syndromes. Then in 1961, the intrathecal route was more widely used to treat arachnoiditis and multiple sclerosis. Epidural therapy again came into general use in 1980 for the treatment of the failed-back syndrome because intrathecal therapy was virtually abandoned after 10 years of spirited scientific controversy. Epidural steroid therapy is now employed extensively, and there are many sanguine reports of its efficacy in treating chronic pain secondary to the failed-back syndrome, but there have also been reports of complications. This review was prompted by recent manufacturer warnings, as well as by an ongoing heated controversy in Australia regarding its use epidurally. During the last 30 years, one can define 5 instructive historical parallels between intrathecal and epidural steroid therapy, and this historicity points up several principles that should govern any further epidural therapy with methylprednisolone acetate. This critical chronologic review surveys neurosurgical use from 1960 to 1970, neurologic use from 1970 to 1980, and anesthesiology use from 1980 to present.