Accurate assessment of a text’s level of translation difficulty is critical for translator training, accreditation and research. Traditionally, people rely on their general impression to gauge a text’s translation difficulty level. If the evaluation process is to be more effective and the results more objective, an instrument needs to be developed. Then two basic research questions must be answered: what to measure and how to measure it. The potential sources of translation difficulty include translation factors (i.e., text difficulty and translation-specific difficulty) and translator factors. Accordingly, to measure translation difficulty, we need to measure text difficulty, identify translation-specific difficulty, and assess translation difficulty (i.e., mental workload) for the translator. Readability formulas are often used to measure text difficulty. The means for identifying translation-specific difficulty include grading translations, analyzing verbal protocols, and recording and analyzing translation behavior. For measuring mental workload, we can adopt subjective measures (e.g., a multidimensional rating scale), performance measures, or physiological measures. This article intends to provide a theoretical and methodological overview of translation difficulty and serve as a foundation for this line of inquiry.