Microhole drilling and microstructure machining with a picosecond (ps) Nd:YVO4 laser (pulse duration of 10 ps) in metals, alloys, and ceramics are reported. Blind and through microholes are drilled by percussion drilling as well as trepanning drilling, where the diameters of the holes are in the range of 20–1000 μm. Microfeatures are also machined and the flexibility of ps laser machining is demonstrated. The quality of drilled holes, e.g., recast layer, microcrack, and conicity, and that of the microstructures, are investigated by an optical microscope, a surface profilometer, or a scanning electron microscope. Ps laser ablation rate is studied by experiments and a simplified laser ablation model.