With a minimal genome containing less than 700 open reading frames and a cell volume < 10% of that of model prokaryotes, Mycoplasma pneumoniae is considered among the smallest and simplest organisms capable of self-replication. And yet, this unique wall-less bacterium exhibits a remarkable level of cellular complexity with a dynamic cytoskeleton and a morphological asymmetry highlighted by a polar, membrane-bound terminal organelle containing an elaborate macromolecular core. The M. pneumoniae terminal organelle functions in distinct, and seemingly disparate cellular processes that include cytadherence, cell division, and presumably gliding motility, as individual cells translocate over surfaces with the cell pole harboring the structure engaged as the leading end. While recent years have witnessed a dramatic increase in the knowledge of protein interactions required for core stability and adhesin trafficking, the mechanism of M. pneumoniae gliding has not been defined nor have interdependencies between the various terminal organelle functions been assessed. The studies presented in the current volume describe the first genetic and molecular investigations into the location, components, architecture, and regulation of the M. pneumoniae gliding machinery. The data indicate that cytadherence and gliding motility are separable properties, and identify a subset of M. pneumoniae proteins contributing directly to the latter process. Characterizations of novel gliding-deficient mutants confirm that the terminal organelle contains the molecular gliding machinery, revealing that with the loss of a single terminal organelle cytoskeletal element, protein P41, terminal organelles detach from the cell body but retain gliding function. The current studies additionally reveal that an intricate balance of transient activation and repression of the gliding machinery is required for normal terminal organelle development and cell division. A second terminal organelle protein, P24, which is normally transcribed with the gene encoding P41, is shown to directly contribute towards this regulation in a P41-dependent manner.