Chemical Alternatives Assessment is a method, rapidly developing for use by businesses, governments and non-government organizations seeking to substitute chemicals of concern in production processes and final products. Chemical alternatives assessment is defined as a process for identifying, comparing and selecting safer alternatives to chemicals of concern (including those in materials, processes or technologies) on the basis of their hazards, performance, and economic viability. The process is intended to provide guidance for assuring that chemicals of concern are replaced with safer alternatives that are not likely to be later regretted. Conceptually the assessment methods are developed from a set of three foundational pillars and five common principles. Based on a number of emerging alternatives assessment initiatives, in this commentary, we outline a chemical alternatives assessment blueprint structured around three broad activities: Scope, Assessment and Selection, and Implementation. Specific tasks and tools are identified for each of these three activities. While it is recognized that on-going practice will further refine and develop the method and tools, it is important that the structure of the assessment process remain flexible, adaptive and focused on the substitution of chemicals of concern with safer alternatives.