The disruption of contrast agent microbubbles has been implicated in novel techniques for high-MI imaging and local drug delivery. At MI>0.6, microbubble fragmentation has been observed with thin-shelled agent (≈10 nm), and shell rupture with thick-shelled agent (≈250 nm). To predict the disruption of these nanoshelled microbubbles, destruction thresholds have been under investigation. In several studies, the Blake threshold pressure was associated with microbubble destruction. The Blake threshold pressure is the peak rarefactional acoustic pressure at which the critical Blake radius is reached, approximately twice the equilibrium radius, above which a bubble behaves like an inertial cavity. We studied the acoustic pressures at which a thin-shelled microbubble fragments and those at which a thick-shelled microbubble cracks. More specifically, we investigated the validity of the Blake threshold for these phenomena. The oscillating and fragmenting behavior of microbubbles with a 10 nm shell was simulated at a driving frequency of 0.5-2 MHz, using a modified Rayleigh-Plesset equation and assuming that fragmentation occurs when the kinetic energy of the microbubble surpasses the instantaneous bubble surface energy. For microbubbles with radii between 1 and 6 µm, the fragmentation thresholds lie between 20 and 200 kPa. Generally, the critical radius is much smaller than twice the equilibrium radius. The moment of break-up during the collapse phase is in agreement with highspeed optical observations that were presented previously. Furthermore, the shell rupture behavior of microbubbles with a thick shell was analyzed for quasistatic pressure changes (relatively low ultrasonic frequencies), assuming that the shell obeys Hooke's Law. The rupture threshold pressure of −80 kPa had been determined from acoustical data. For shells with the typical Young's modulus 2 MPa and Poisson ratio 0.5, this is in agreement with the observation that the maximal excursion upon rupture of such bubbles is smaller that 0.3 µm. In conclusion, we may state that the Blake threshold is neither a good estimator for the fragmentation, nor for the rupture of contrast agent microbubbles.