Classroom observation research plays an important role in policy, practice, and scholarship for students with disabilities. When interpreting results of observation studies, it is important to consider the validity evidence provided by researchers and how that speaks to the intended use of those results. In this literature synthesis, we used Kane’s argument-based approach to validity to describe evidence of validity for uses of observation instruments in classroom observation research regarding teachers of students with disabilities. We identified 102 studies from 1975 to 2020 that met inclusion criteria. Results indicated many studies did not report validity evidence to support their use of the observation instruments. Over time, reporting levels for much of the evidence has remained relatively constant, but we noted a consistent decrease in number of observations conducted per teacher and a consistent and large increase in reporting of teacher participant characteristics. We provide implications of this for research and practice and suggestions for improving classroom observation research.