Augusto and Michaela Odone (Nick Nolte and Susan Sarandon) are the adoring parents of a bright little boy who inexplicably develops alarming behavioral problems, after they return from working in the Comoro Islands. A series of investigations results in a diagnosis of adrenoleukodystrophy (ALD), but the boy rapidly deteriorates into a bed-ridden, inarticulate state. Frustrated by the medical profession's inability to help, Augusto and Michaela embark on an odyssey of salvation, studying lipid metabolism, promoting international conferences, and trying to disseminate their findings to other parents.

Their insights lead them to experiment with at least two effective therapies, one of which is erucic acid (Lorenzo's oil). Michaela feels guilt as well as grief, when she understands that the X-linked disease is passed from mother to son. In an effort to keep Lorenzo at home, she refuses to admit the extent of his disability, alienates her family, dismisses nurses, and assumes most of the care herself, nearly ruining her own health and her marriage. The film ends hopefully with tiny signs of recovery in Lorenzo. The credits roll over the faces and voices of happy, healthy-looking boys who have been taking Lorenzo's Oil.