Development of new tools and instruments helps drive scientific progress. Recent development of specialized tools has led to new levels of understanding of matter by helping scientists detect, manipulate, isolate, measure, fabricate, and investigate nanoscale matter with unprecedented precision and accuracy. This chapter describes four major learning goals that are associated with the Tools and Instrumentation big idea. Focus can be placed on different aspects of the learning goals depending on the grade level and science context (chemistry, physics, Earth science, or biology).