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Ayurvedic texts recognise that drugs may be unavailable and prescribe approved substitutes, pratinidhi or abhava pratinidhi dravya, to be used in their place. The practice has become more important as many classical drugs, particularly Himalayan and orchid species, have become rare or threatened. This review examines the classical rationale for substitution, summarises studies that have tested the equivalence of classical substitute pairs, and proposes standards for evaluating substitutes. Classical substitution rests on shared Dravyaguna properties and actions rather than on botanical relationship. The best-studied example is Musta (Cyperus rotundus), a common weed, as a substitute for Ativisha (Aconitum heterophyllum), a rare Himalayan plant. The two are botanically unrelated, yet similar in classical properties, phytochemical profile and antidiarrhoeal activity. An analysis of 223 substitutes for 122 drugs in Rhazes’ Unani compendium Kitab al-Abdal found that about 76% were consistent with Ayurvedic and Unani property-based principles. Compilations of substitutes from Ayurvedic texts list many more pairs, but most have not been tested. The Ashtavarga group, several of whose members are orchids that are rare or of uncertain identity, is routinely replaced with other drugs in commercial formulations, often without comparative evidence. We argue that substitution should be judged by equivalence for a defined indication. That requires pre-specified criteria based on classical properties, chemical markers and relevant pharmacological or clinical endpoints, using authenticated and characterised material. Evaluated in this way, pratinidhi dravya offer a principled route to conserving threatened species without compromising therapy.