Despite an available vaccine and effective antibiotics, Mycobacterium tuberculosis is still the causative agent of almost 2 million deaths every year. The cell wall of M. tuberculosis is composed of sugars and lipids of exotic structure, many of which contribute to its pathogenicity. The majority of the enzymes responsible for building this structure are essential. However, they share very little homology with well-characterized enzymes, which makes their identification in the genome difficult. Despite this, our knowledge of the structure of the cell wall of M. tuberculosis is fairly complete and an increasing number of genes have been identified that are involved in its biosynthesis. By contrast, data concerning regulation of the expression of these genes and control of the cell wall composition are restricted. This review summarizes current information on the genetics of cell wall biosynthesis in M. tuberculosis, incorporating available data on gene organization and regulation.