Suitable dosage forms are not always available for specific patient populations and must be extemporaneously compounded. Extemporaneous preparation is the manipulation of drugs and excipients for a particular patient using traditional compounding techniques; these are referred to as ‘off-label’ and ‘unlicensed’ medicines. Off-label use can include altered doses, dosage forms or indications for use. Registered medicines are produced to internationally recognized standards of Good Manufacturing Practices. Within the pharmaceutical manufacturing industry, quality, safety and efficacy are enforced by regulatory legislations. In contrast, the responsibility for acceptable standards for the compounding of ‘off-label’ medicines falls on the prescriber, pharmacist or hospital nurse. Studies have been conducted by researchers from Australia and throughout Europe, highlighting the frequency of off-label use for paediatrics, with one study reporting that most extemporaneous preparations (29.6%) were for drugs required to treat metabolic diseases. Risks include compounding errors, adverse reactions to ingredients and excipients, and non-validated stability of the product. Sterile compounded products, including products for ophthalmic and palliative care, carry additional risks in these vulnerable patients. This paper provides an overview of off-label medicines highlighting biopharmaceutical, quality, safety and efficacy issues important to medical and allied health professionals.