Alignment to the Next Generation Science Standards (NGSS) is essential in efforts to interpret the standards and to compare curriculum, pedagogy, and assessment efforts with respect to the standards. However, relatively little work has explored the alignment implications of NGSS. This article is a conceptual analysis that gives an overview of alignment definitions and methods, and then explores how alignment has been explicitly or implicitly described in extant work on interpretation of NGSS. The purpose is to highlight challenges that remain to be addressed for ensuring alignment for curriculum, assessment, and pedagogy under NGSS. Four challenges for alignment and interpretation research on NGSS are discussed: (1) What are the appropriate referents and comparands for judging alignment under NGSS? (2) How is alignment for integrated standards to be defined and judged? (3) What is the appropriate idea of focus in NGSS? (4) What role do learning progressions, and alignment with respect to them, play for interpreting NGSS?