A standard of care, or best practice, is a guideline for the appropriate treatment of a condition, as established by formal or informal consensus among experts on that condition. Basically, the standard of care for the treatment of a disease is whatever most physicians agree is the best way to treat that disease.

In the context of a clinical trial, a patient receiving treatment at the standard of care will be treated with the same drugs they would receive for their condition were they being treated outside of a clinical trial. In this way, researchers can measure the impact of an experimental drug against that of existing treatment.

Where multiple treatments for a condition exist, guidelines and medical practice often distinguish first-line therapies from second-line therapies (and sometimes third- or more). The first-line therapy for a given disease is the one that most physicians will prescribe to previously untreated patients, usually due to a combination of high effectiveness and low comparative risk. If that therapy is ineffective, physicians will move on to a second-line therapy. Because different treatments for the same condition often employ different mechanisms, interact differently with other medications, and cause different side effects, second- or third-line therapies can sometimes benefit patients when first-line therapies cannot. This is one of the reasons it can be helpful to have multiple drugs intended to treat the same disease.