We present photoacoustic shadow-casting microscopy (PASM), a technique that allows high-resolution imaging of weakly absorbing biological samples with unprecedented sensitivity. In PASM, a uniform optical absorbing layer is placed in contact with the samples and is excited by the light transmitted through the sample, producing photoacoustic (PA) waves with an increased signal-to-noise ratio compared with that generated by the sample itself. Therefore, given a desired image quality, the required excitation fluence is much reduced, alleviating the photothermal damage to the specimen. The system provides a lateral resolution of 5 μm when using a 0.30 NA microscope objective lens. To demonstrate PASM, we present images of bovine red blood cells and microbeads.