First Do No Harm is the first line of the Hippocratic oath that all doctors must swear, and has cognates in Buddhism. However, in many cases, doctors hesitate or refuse to recommend harmless treatments, not because those might do something amiss, but because their efficacy isn't yet supported by scientific research.

Four-year-old Robbie (Adkins) is diagnosed with a type of epilepsy for which the cause is unknown, and his parents, Lori (Streep) and Dave (Ward), agree to a series of excruciating drug treatments, but those only seem to worsen his condition; their situation is complicated when their health coverage lapses. Then Lori learns of the Ketogenic Diet: a third of epileptic children on it endure no more seizures. Robbie's parents are furious that his doctor (Janney) failed to tell them about the diet and refused to help them try it; instead, she recommends brain surgery. The film demonstrates the lengths to which families sometimes must go to take control of their loved ones' health. First Do No Harm presents a blistering attack on the rigid, insensitive western medical establishment.