This chapter examines the economic dimensions of the transition from traditional animal testing to New Approach Methodologies (NAMs) in safety sciences. Drawing on data from regulatory agencies, industry trends, and technological innovations, it articulates how ethical motivations have been joined—if not eclipsed—by compelling economic, scientific, and policy rationales for replacing animal-based testing. It evaluates the comparative cost structures of in vivo versus in vitro/in silico methods, market mechanisms relevant to this field, and other socioeconomic analyses of the (lack of) progress in this field. Special attention is paid to the implications of REACH regulation in Europe, the accelerating regulatory shift in the United States (particularly under the FDA’s new roadmap), and the disruptive role of artificial intelligence (AI) in reshaping toxicology as a data-driven science. The chapter concludes by framing alternatives to animal testing not as regulatory burdens but as economic opportunities, essential for global competitiveness, scientific integrity, and ethical responsibility.