||Molecular oxygen (O2) has a multitude of important biological roles. It is also a useful marker of cell/tissue function and readout parameter which can report on changes in cell metabolism and bioenergetics, tissue (patho)physiology, responses to drug treatment and other stimuli. Various in vitro, ex-vivo and in vivo cell and tissue models are currently used in biomedical research, however for many of them control of sample oxygenation and cellular O2 levels is inadequate. Phosphorescence based O2 sensing technologies can address these challenges and provide convenient and versatile means for direct, real-time, quantitative monitoring of O2 levels in various compartments of complex biological samples, including in situ monitoring of cellular O2 and high-resolution mapping O2 concentration in 3D. A number of advanced O2 sensing and imaging platforms have been developed in recent years, which operate with solid-state sensors, soluble probes or imaging nanosensors and in conjunction with portable handheld instruments, commercial plate readers and sophisticated live cell imaging platforms. I will provide examples how these sensor systems can be used in physiological studies with simple 2D cell models, more complex micro-tissue models (multicellular spheroids, heterocellular organoids, cultured tissue slices), live animals, and with common disease models such as hypoxia, cancer, inflammation.