Poor drug delivery across capillaries and poor penetration into the extracellular matrix are often the rate limiting factors in drug efficacy leading to several failed clinical trials. I will describe a method to noninvasively and locally open capillaries by using ultrasound and systemically-administered microbubbles to treat neurological disorders and cancer. I will then discuss a new technology, which can spatially and temporally monitor these procedures in real-time. First, drug delivery to the brain is limited by the blood-brain barrier, which excludes nearly all luminal compounds greater than 400 Da from entering the extracellular matrix. I will describe our approach to noninvasively and locally opening the blood-brain barrier in vivo and demonstrate not only the delivery of large therapeutic compounds to neurons, but also the induction of downstream cellular activity through the delivery of neurotrophic factors. Second, cancer therapy is limited by poor vascularity and a dense extracellular matrix preventing poor drug penetration following extravasation. I will describe our approach to generate a high mechanical stress event, which led to the dispersion and deep penetration of self-replicating adenoviruses throughout the tumour. This resulted in reduced tumour growth rates and longer mouse survival. Third, while the noninvasive feature of ultrasound provides several advantages, it has also made it difficult to monitor and control therapeutic activity occurring deep in the body. I will describe a passive acoustic mapping approach, which can spatially and temporally monitor our techniques in real-time.