The textile industry sees currently a fast development of legal and voluntary restrictions of chemicals content in textile products. However, the on-going phase-out work focuses on evaluating the environmental and health aspects of chemicals. The technical performance in the end application for the chemical does not receive the same attention. In addition, many research projects committed to evaluating hazardous substances and their possible alternatives also neglects the technical performance. The technical performance is left to the companies to evaluate. This may lead to inefficiency in the substitution process and also have the consequence that companies never dare to take the step to practical substitution, at least not in a proactive way. This chapter presents a model for practical substitution, developed and evaluated in several case studies, whereof two in the textile field: water and soil repellent textile coating materials and flame retarded textiles. From the general lessons learnt, an improved substitution methodology with widespread applicability has been defined.