Off-label uses of drugs are increasingly at the forefront of discussions both in the patients’ forum and also in the physician’s forum. Off-label drug use refers to the prescription of an approved and marketed medication in a manner that is different from what is approved on the label. The common types of off-label use are the use of a drug for a different indication, different dose, different duration, different route of administration, or different patient population. Off-label drug use is very common and accounts for one-fifth or 20% of all prescriptions and in some cases, it can be very high even up to 80%. When appropriately prescribed, off-label drug use has many advantages and can further the cause of science by discovering new innovative uses for existing drugs. It can also help the physician in providing optimum health care in many diseases/patient groups. However, inappropriate off-label use may expose the patient to a higher risk of adverse effects and potential harm. Off-label drug use demands a heightened standard of care and whenever a physician uses a drug in an off-label manner, the decision must be based on sound scientific evidence and the patient should be made a partner as part of the “shared decision making.”