The publication of A Framework for K-12 Science Education (National Research Council, 2012) and the Next Generation Science Standards (NGSS Lead States, 2013) have created a need for new alternate content standards and alternate assessments in science that are linked to the new general education science standards. This article describes how a consortium of four states used Evidence-Centered Design (Mislevy, Steinberg, & Almond, 2003) and Universal Design for Learning (CAST, 2012) to develop alternate science content standards and assessments. A set of 43 alternate science content standards was created and an alternate assessment at each of three grade spans. Evidence that supports appropriateness of the alternate standards for students with SCD and fidelity of representation of the Framework is presented. One cycle of testlet/item development was conducted. Results of a pilot test (251 items; 1,606 students) are presented. Evidence for validity and accessibility of the alternate assessment is presented. Major findings include that the assessment items met accessibility, bias and sensitivity, and content requirements, and that students were able to understand and respond to assessment items. Data from a pilot assessment provided evidence of the accessibility of the standards and assessments. The implications of this work for teaching science to students with SCD and preliminary efforts to develop supports for teachers are discussed.