Optoacoustic (photoacoustic) diagnostic modality is a technique that combines high optical contrast and ultrasound spatial resolution. We proposed using the optoacoustic technique for a number of applications, including cancer detection, monitoring of thermotherapy (hyperthermia, coagulation, and freezing), monitoring of cerebral blood oxygenation in patients with traumatic brain injury, neonatal patients, fetuses during late-stage labor, central venous oxygenation monitoring, and total hemoglobin concentration monitoring as well as hematoma detection and characterization. We developed and built optical parametric oscillator-based systems and multiwavelength, fiber-coupled highly compact, laser diode-based systems for optoacoustic imaging, monitoring, and sensing. To provide sufficient output pulse energy, a specially designed fiber-optic system was built and incorporated in ultrasensitive, wideband optoacoustic probes. We performed preclinical and clinical tests of the systems and the optoacoustic probes in backward mode for most of the applications and in forward mode for the breast cancer and cerebral applications. The high pulse energy and repetition rate allowed for rapid data acquisition with high signal-to-noise ratio from cerebral blood vessels, such as the superior sagittal sinus, central veins, and peripheral veins and arteries, as well as from intracranial hematomas. The optoacoustic systems were capable of automatic, real-time, continuous measurements of blood oxygenation in these blood vessels.