Clinical in-vivo electrophysiological measurements using standard technologies provide spatial resolution limited by the number of electrodes. Recent strategies demonstrate that high resolution is possible by use of active multiplexing silicon electronics, in flexible forms capable of integration with soft, curvilinear tissues of the body. In vivo cardiac mapping experiments with such technology illustrate in-situ mapping of the spread of electrocardiogram (ECG) waveforms from natural and paced beats. In other examples, circuits in ultrathin mesh formats on sheets of bioresorbable substrates of silk fibroin improve the ability of these systems to conformally wrap the tissue. Neural mapping experiments on feline animal models illustrate the utility of this approach. These concepts provide capabilities for implantable diagnostic and therapeutic systems, which cannot be realized with conventional, wafer-scale device designs.