Abilities in scientific thinking and reasoning have been emphasized as core areas of initiatives, such as the Next Generation Science Standards or the College Board Standards for College Success in Science, which focus on the skills the future will demand of today's students. Although there is rich literature on studies of how these abilities develop in students across grade levels, the research community has not reached consensus on their definition, modeling, or assessment. To advance research in this important area, a coherent theoretical model of scientific reasoning is needed for practically guiding instruction and assessment. For decades, the only instrument available for large-scale application was the Lawson's Classroom Test of Scientific Reasoning, but the instrument has demonstrated validity weaknesses and ceiling limitations, and its design is missing an explicit modeling framework for justifying the included skills. As a result, there is an urgent need for the development of a comprehensive modeling framework of scientific reasoning and a valid scientific reasoning assessment that targets the wide-ranging skills required for 21st century learners. This paper reports on the development of a modeling framework of scientific reasoning along with a new assessment instrument, adding to the research literature in a much needed area. The modeling framework integrates research in scientific and causal reasoning and operationally defines the skills and subskills that underlie the reasoning for knowledge development through scientific inquiry. Subsequently, this framework is used to guide the development of an assessment instrument on scientific reasoning. The validity and reliability of the instrument, which have been established based on large-scale testing, will also be discussed.