Tuberculosis (TB) continues to threaten many peoples’ health worldwide, regardless of their country of residence or age. The current diagnosis of TB still uses mainly traditional, time-consuming, and/or culture-based techniques. Efforts have focused on discovering new biomarkers with higher efficiency and accuracy for TB diagnosis. Proteomics—the systematic study of protein diversity—is being applied to the discovery of novel protein biomarkers for different types of diseases. Mass spectrometry (MS) technology plays a revolutionary role in proteomics, and its applicability benefits from the development of other technologies, such as matrix-based and immune-based methods. MS and derivative strategies continuously contribute to disease-related discoveries, and some promising proteomic biomarkers for efficient TB diagnosis have been identified, but challenges still exist. For example, there are discrepancies in the biomarkers identified among different reports and the diagnostic accuracy of clinically applied proteomic biomarkers. The present review summarizes the current status and future perspectives of proteomics in the field of TB biomarker discovery and aims to elicit more promising findings for rapid and accurate TB diagnosis.