Lipid-coated microbubbles are of particular interest in biomedical applications as ultrasound contrast agents, drug and gene delivery vehicles, and blood substitutes. In this study, we report on the collapse and shedding behavior of the lipid monolayer coating a microbubble using fluorescence microscopy. Isotropic monolayer compression was induced by the dissolution of air-filled, lipid-coated microbubbles in degassed media. In addition, the gas transport properties of the monolayer were inferred from microbubble dissolution rates and shell resistances were determined by comparing experimental data to the modified Epstein-Plesset equation. Further studies on the surface behavior of mixed monolayers under anisotropic compression at room temperature were performed using a Langmuir trough. The monolayer shell was comprised of saturated diacyl phosphatidylcholine (C14:0–C20:0) and DiC18PE-PEG 2000. Results indicate that the collapse pressure of the mixed monolayer is higher than the collapse pressure of the pure components for the case of C14:0 and monotonically decreases with increasing number of carbons per chain of the main lipid component. Fluorescence microscopy imaging of these mixed monolayers were also performed. For coated microbubbles, the morphology of monolayer collapse structures and shed particles as well as shell resistances were monitored as a function of phospholipid acyl chain length (n) at room temperature. The two components generally formed a single miscible phase when n=14 while a significant portion of this microbubble population displayed phase separation. For these microbubbles, the dissolution was smooth and symmetrical and the monolayer collapse occurred via shedding of sub-optical particles, vesicles, and tubes. Conversely, two-phase coexistence was observed when n>14. For these bubbles, the dissolution was asymmetrical and collapse involved the propagation of monolayer folds and loss of bubble sphericity. For very rigid monolayers, substantial surface buckling was observed with simultaneous nucleation and growth of folds. The folds formed and propagated across the shell until the entire excess lipid was shed in a single event such that the shell smoothed and bubble sphericity was generally restored.