In addition to the use in cardiovascular diagnostic procedures, microbubbles (MBs) have potential in diagnosis of tumours, vascular and blood flow abnormalities, as well as for targeted, ultrasound-triggered drug delivery and as intravascular mechanical devices. All commercial soft, phospholipid-shelled MBs contain a fluorocarbon (FC) gas. Both experimental data and theoretical models confirm that the cohesion pressure in phospholipid monolayers is decreased by FCs, supporting a strong shell film fluidizing effect. The co-surfactant activity of FC gases towards MB shell components or therapeutic cargos, including polymers, proteins, fluorinated drugs, biomarkers and tracers, will be discussed. A new approach allowed immobilization of fluorinated tracers in phospholipid-shelled MBs. Perfluorohexane allowed preparation of stable spherical hydrophobin HFBII-coated MBs, while only inadequate mixtures of aggregates and elongated MBs are obtained under air. Nanodiamonds, iron oxide and cerium oxide nanoparticles can be driven to the air/water interface when exposed to a FC vapor. This new phenomenon enables production of stable nanoparticle-shelled MBs without need for a surfactant. Such microbubbles have potential as multimodal contrast agents (MRI, optical, photoacoustics, PET/ultrasound), as image-guided delivery systems for ultrasound-mediated cancer treatment, and for cell labelling and imaging. (1) M. P. Krafft and J. G. Riess, Adv. Colloid Interface Sci. 294, 102407 (2021).