Ultrasound and microbubble induced blood-brain barrier opening has shown success in clinical trials as a promising method to deliver drugs to the brain. Shelled gas bubbles, a few micrometres in diameter, are administered intravenously, and distribute throughout the cardiovascular system. When ultrasound is applied to the brain, the microbubbles expand and contract within the vasculature, temporarily disrupting the blood-brain barrier, and allowing drugs to pass through. While this technique has been shown to be effective at delivering drugs, its mechanisms remain relatively poorly understood. Better understanding how microbubbles interact with tissues could enable refinement of therapies. This thesis investigates the fundamental physical interactions between microbubbles and soft tissues using two distinct but related experimental platforms that utilise high-speed microscopy. Firstly, microbubbles within soft tissue-mimicking hydrogel channels are observed during exposure to typical therapeutic ultrasound pulses. The primary radiation force is shown to be significant, and can cause bubbles to deform the soft gels by several micrometres. Microbubbles are also investigated in brain tissue, using acute cortical slices from the brains of juvenile rats, transcardially perfused post-mortem with a concentrated solution of SonoVue®. This technique is shown to be an effective method of observing microbubbles using optical microscopy within the microvasculature of live brain tissue. Radial oscillations of bubbles within brain microvessels can deform surrounding tissue at both microsecond and millisecond time scales. Extravasation of microbubbles due to the primary radiation force can occur during typical ultrasound pulses, and is common at higher ultrasound pressures (mechanical index of 0.6 and above). These results demonstrate the significance of both radial oscillations and the primary radiation force as ways in which microbubbles can physically impact their surroundings. Additionally, acute brain slices are shown to be a valuable tool to investigate microbubble behaviours and mechanisms of drug delivery in a physiologically relevant environment.