Essentially, all cellular functions are executed by proteins. Different physiological and pathological conditions dynamically control various properties of proteins, including expression levels, post-translational modifications (PTMs), protein–protein interactions, enzymatic activity, etc. Thus far, the vast majority of proteomic efforts have been focused on quantitative profiling of protein abundance/expression and their PTMs. In this article, we review some recent exciting progress in the development of proteomic approaches to examine protein functions from perspectives other than expression levels and PTMs. Specifically, we discuss advancements in proximity-based labeling, analysis of protein termini and newly synthesized proteins, and activity-based protein profiling.