This paper examines one specific aspect of the compounding—sunthesis in Greek—of remedies in ancient pharmacy, namely the substitution of one or several of the ingredients stipulated in the original recipe. This aspect has both positive and negative facets. The positive is the art of substitution, which should theoretically rely on sufficient knowledge of the powers of ingredients to replace like for like. The negative facet is the implication of the potential for fraud or adulteration, which led to the development of tests to determine the authenticity of a given preparation or its ingredients. The paper examines the boundary between substitution and fraud and assesses the roles that these two phenomena played in the development of ancient pharmacy.