Imaging three-dimensional structures represents a major challenge for conventional microscopies. Here we describe a Spatial Light Modulator (SLM) microscope that can simultaneously address and image multiple targets in three dimensions. A wavefront coding element and computational image processing enables extended depth-of-field imaging. High-resolution, multi-site three-dimensional targeting and sensing is demonstrated in both transparent and scattering media over a depth range of 300-1,000 microns.