The pathogen Mycobacterium tuberculosis (Mtb), causing tuberculosis disease, features an extraordinary thick cell envelope, rich in Mtb-specific lipids, glycolipids, and glycans. These cell wall components are often directly involved in host-pathogen interaction and recognition, intracellular survival, and virulence. For decades, these mycobacterial natural products have been of great interest for immunology and synthetic chemistry alike, due to their complex molecular structure and the biological functions arising from it. The synthesis of many of these constituents has been achieved and aided the elucidation of their function by utilizing the synthetic material to study Mtb immunology. This review summarizes the synthetic efforts of a quarter century of total synthesis and highlights how the synthesis layed the foundation for immunological studies as well as drove the field of organic synthesis and catalysis to efficiently access these complex natural products.